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1.  Cyclosporine A as a Primary Treatment for Panniculitis-like T Cell Lymphoma: A Case with a Long-Term Remission 
Subcutaneous panniculitis-like T cell lymphoma (SPTL) is a distinctive cutaneous lymphoma characterized by an infiltration of subcutaneous tissue by neoplastic T cells, similar to panniculitis. It is well-established that patients who are diagnosed with SPTL usually respond poorly to chemotherapy, showing fatal outcome. As a first line treatment for SPTL, anthracycline-based chemotherapy was most frequently used. For the treatment of SPTL, the efficacy of cyclosporine A has been recently reported in relapsed SPTL after anthracycline-based chemotherapy. However, it is still not clear whether cyclosporine A can be used as a first-line treatment against SPTL. Here, we report a case of SPTL, which achieved complete remission for nine years after first-line cyclosporine A therapy. This study suggests that cyclosporine A can induce a complete long-term remission as a first-line treatment.
PMCID: PMC4132451  PMID: 25038767
Subcutaneous panniculitis-like T cell lymphoma; Cyclosporine A; Remission
2.  Successful Treatment of Disseminated Subcutaneous Panniculitis-Like T-Cell Lymphoma with Single Agent Oral Cyclosporine as a First Line Therapy 
Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare cutaneous neoplasm of mature cytotoxic T-cells. Currently there are no standardized therapies for SPTL; however good responses have been seen with chemotherapy regimens generally employed for B-cell lymphomas. Cyclosporine, an immunosuppressant, has shown good responses in relapsed/refractory SPTL; however its use in first line setting is not well established. We, herein, describe a 22-year-old girl with disseminated SPTL who attained complete clinical remission with single agent oral cyclosporine used as a first line therapy.
PMCID: PMC4259071  PMID: 25506440
3.  Bexarotene Is Active Against Subcutaneous Panniculitis-Like T-Cell Lymphoma in Adult and Pediatric Populations 
Subcutaneous panniculitis-like T-cell lymphoma (SPTL-AB) and cutaneous gamma/delta T-cell lymphoma (CGD-TCL) are rare cutaneous T-cell lymphomas for which no standard treatment exists. We report our experience with bexarotene, an oral retinoid, in 15 adults and children with these disorders. In this series, we found a 77% overall response rate of bexarotene with limited toxicity for these disorders.
Subcutaneous panniculitis-like T-cell lymphoma (SPTL-AB) and cutaneous gamma/delta T-cell lymphoma (CGD-TCL) are rare T-cell lymphomas with varying clinical courses. There is no standard treatment, although chemotherapy and hematopoietic stem cell transplantation are commonly used. We describe results using bexarotene for children and adults with these disorders.
We identified 15 patients (12 adults, 3 children) who were treated with bexarotene between 2000 and 2010 from the Memorial Sloan-Kettering Cancer Center lymphoma database, the Stanford Cancer Center Registry, and the National Cancer Institute (NCI) pediatric lymphoma database. There were 8 females and 7 males, with a median age of 45 years (range, 3 years to 85 years). All patients had stage IV disease. Two of 15 and 4 of 15 patients had documented CGD-TCL and SPTL-AB, respectively; others were presumed to have SPTL-AB. Bexarotene was administered at flat doses corresponding to 91 to 339 mg/m2/d. Two of 15 patients received concurrent denileukin diftitox. Two children received bexarotene as maintenance therapy and were not evaluable for response.
Among those treated with bexarotene alone, the overall response rate (ORR) was 82% (6/11 complete response [CR], 3/11 partial response [PR]). One of the 2 patients treated with concomitant denileukin diftitox responded for an ORR of 10/13 (77%), including 54% CR and 23% PR. Median progression-free survival was 38.4 months; median duration of response was 26.3 months. Six patients developed hypothyroidism and 9 developed hyperlipidemia; one patient developed dose-limiting hypertriglyceridemia. One pediatric patient developed insulin-dependent diabetes mellitus.
In this retrospective series, bexarotene showed a high response rate in SPTL-AB and CGD-TCL. It was generally well-tolerated with durable responses; therefore, bexarotene represents a promising therapy for children and adults with these disorders.
PMCID: PMC3938280  PMID: 22001256
Bexarotene; Cutaneous gamma/delta T-cell lymphoma; Subcutaneous panniculitis-like T-cell lymphoma
4.  Subcutaneous Panniculitis-Like T-cell Lymphoma: A Clinical and Pathologic Study of 14 Korean Patients 
Annals of Dermatology  2011;23(3):329-337.
Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a distinctive skin lymphoma characterized by neoplastic T-cell infiltration of the subcutaneous tissue, mimicking panniculitis.
To describe the clinical and pathologic features of SPTL in Korean patients.
Fourteen SPTL patients evaluated over 15 years were retrospectively reviewed.
The mean patient age was 35 years (range: 7~73 years), with male predominance (2.5:1). Most patients presented with either nodules or plaques, occurring most commonly on the trunk, with two patients (14%) having hemophagocytic syndrome. Histopathologically, all patients showed infiltrates of small-to-medium pleomorphic cells mimicking panniculitis, with some also showing rimming, bean-bag cells, and fat necrosis. Most patients were positive for CD3 (14/14), CD8 (12/13), TIA-1 (9/9) and βf1 (5/5), but were negative for CD4 (11/12), CD20 (8/8), CD56 (14/14) and Epstein-Barr virus (8/8). Ten patients (71%) received chemotherapy and 2 (14%) died due to the disease, with an average survival time of 4 months. Survival analysis did not reveal any significant prognostic factors.
This is the first series of patients with SPTL in Korea. Due to its indolent clinical course and relatively high survival rate, SPTL should be differentiated from cutaneous γδ T-cell lymphoma.
PMCID: PMC3162262  PMID: 21909203
Subcutaneous panniculitis-like T-cell lymphoma
5.  Successful Treatment of a Panniculitis-Like Primary Cutaneous T-Cell Lymphoma of the α/β Type with Bexarotene 
Case Reports in Dermatology  2012;4(1):56-60.
Subcutaneous panniculitis-like T-cell lymphoma (SPTL) of the α/β type is a rare subtype of non-Hodgkin's lymphoma of the skin. Although these tumors usually run an indolent course, disease-related morbidity is often severe. Clinical findings include subcutaneous tumors located on the extremities or trunk, often accompanied by systemic symptoms like fever or fatigue. Due to the low incidence of SPTL, no standardized therapy has been defined so far and there is currently no curative therapy available for this type of non-Hodgkin's lymphoma. By sharing our experience with bexarotene therapy, we present a safe and potentially improved treatment for patients with SPTL. In the case presented, bexarotene was able to induce remission even after recurrence of disease.
PMCID: PMC3339687  PMID: 22548037
Cutaneous T-cell lymphoma; Lymphoma; Panniculitis; Therapy; Retinoids; Bexarotene
6.  Subcutaneous panniculitis-like T-cell lymphoma in a patient with long-term remission with standard chemotherapy. 
Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a very rare postthymic T-cell non-Hodgkin's lymphoma with poor prognosis. There is not a standard treatment for this disease. Here we describe the first case of SPTL with unusual periorbital involvement, pancytopenia, hepatic dysfunction and coagulopathy, which was successfully treated with a chemotherapy regimen of cyclophosphamide, hydroxydaunomycin (doxorubicin), Oncovin (vincristine) and prednisone (CHOP). Our case demonstrates that although the natural history of SPTL is aggressive, patients may respond effectively to combination chemotherapy. Early recognition of the classic subcutaneous lesions and its associated systemic signs, such as unusual periorbital involvement, liver dysfunction and hemophagocytic syndrome, is very important in managing this aggressive lymphoma. Immunohistochemical and genetic studies are helpful in confirming the diagnosis. Early initiation of aggressive chemotherapy is recommended for better clinical outcome.
PMCID: PMC2574403  PMID: 17987923
7.  Molecular characterization of subcutaneous panniculitis-like T-cell lymphoma reveals upregulation of immunosuppression- and autoimmunity-associated genes 
Subcutaneous panniculitis-like T cell lymphomas represent a rare and difficult to diagnose entity of cutaneous T cell lymphomas. SPTL affects predominantly young adults and presents with multifocal subcutaneous nodules and frequently associated autoimmune features. The pathogenesis of SPTL is not completely understood.
The aim of this study was to unravel molecular pathways critical to the SPTL pathogenesis. Therefore, we analyzed 23 skin samples from 20 newly diagnosed SPTL patients and relevant control samples of adipose and non-malignant panniculitis tissue by using gene expression microarray, quantitative PCR, and two-colour immunohistochemistry.
Interestingly, indoleamine 2,3-dioxygenase (IDO-1), an immunotolerance-inducing enzyme, was among the most highly overexpressed genes in all comparisons. The expression of Th1-specific cytokines, known to be associated with autoimmune inflammation (i.e. IFNG, CXCR3, CXCL9, CXCL10, CXCL11, and CCL5), were also significantly increased. Confirmed using immunohistochemistry, the morphologically malignant lymphocytes expressed CXCR3 and CXCL9. IDO-1 expression was found both in some morphologically malignant lymphocytes rimming the adipocytes and in surrounding CD11c− CD68− cells but not in CD11c+ dendritic cells in the microenvironment. The proportion of FoxP3+ cells in SPTL exceeded that in the benign panniculitis samples.
Our results indicate that the up regulation of the tolerogenic IDO-1 together with the up regulation of IFNG, CXCR3 ligands, and CCL5 are features of SPTL lesions. We anticipate that the IFNG-inducible IDO-1 expression contributes to the formation of an immunosuppressive microenvironment, favorable for the malignant T cells. This study provides a relevant molecular basis for further studies exploring novel therapeutic means for subcutaneous T cell lymphoma.
Electronic supplementary material
The online version of this article (doi:10.1186/s13023-014-0160-2) contains supplementary material, which is available to authorized users.
PMCID: PMC4320460  PMID: 25928531
Subcutaneous panniculitis-like T-cell lymphoma; IDO-1; Immunosuppressive tumor microenvironment; Th1-type
8.  Subcutaneous Panniculitis-Like T-Cell Lymphoma (SPTL) in a Child with Spontaneous Resolution 
Subcutaneous panniculitis-like T-cell lymphomas (SPTLs) α/β are rare in childhood. The present report refers to a case of a 7-year-old male child presenting an extensive skin lesion that began when he was 5 years of age. Two biopsies were evaluated using the CD3, CD4, CD8, CD56, βF1, and TIA markers. A dense infiltrate of CD3+, CD4−, CD8+, CD56−, βF1+, and TIA+ pleomorphic lymphocytes was found in the subcutis. The previous biopsy showed cytophagic histiocytic panniculitis with a small focus on CD8+ and βF1+ malignant cells. The lesion regressed spontaneously. This case shows that prognosis may be excellent in SPTL (α/β). On the other hand, it also serves as an alert that a biopsy performed in an area of cytophagic panniculitis may lead to misdiagnosis.
PMCID: PMC3350120  PMID: 22606445
9.  Relapse of lymphoma after allogeneic hematopoietic cell transplantation: Management strategies and outcome 
The outcome and management of relapsed lymphoma after allogeneic hematopoietic cell transplantation (HCT) is difficult. Therapeutic options may include donor lymphocyte infusion (DLI), reduction of immunosuppression (RIS), chemotherapy, radiation, immunotherapy, second HCT and experimental treatments, but reported data contrasting the response and efficacy of these salvage treatments is limited. We describe the treatments, response, prognosis and long-term survival of 72 patients with relapse of lymphoma after allogeneic HCT.
Between 1991 and 2007, 227 lymphoma patients underwent allogeneic HCT. Of these, 72 (32%) developed relapse/progression after their HCT at a median of 99 days (0–1898 days); 37 had early (<100 days) post-HCT relapse. Forty-four had non-Hodgkin's lymphoma (7 mantle cell, 5 indolent, 15 diffuse large B cell, 4 Burkitt's and 13 T/Natural Killer cell) and 28 patients had Hodgkin's lymphoma. At the time of HCT, 62 patients were in remission (22 in complete [CR] and 40 in partial [PR]), one had stable while 9 had progressive disease. Seventeen cases received myeloablative and 55 received a reduced intensity conditioning regimen. At relapse, most patients had generalized lymphadenopathy, extranodal organ involvement and advanced disease. Five patients received no intervention for the post-HCT relapse. Immunosuppressive treatment was reduced or withdrawn as the first line therapy in 58 patients (80.5%); 47 were treated using combinations of conventional chemotherapy (n=22), rituximab (n=27), interferon (IFN) (n=1), DLI (n=7), second HCT (n=2), local radiation (n=23) and other therapy (n=6). Thirty-eight patients had an objective response (CR in 30, PR in 8) and 2 had stable disease (SD). At the post-HCT relapse, favorable prognostic factors for survival after HCT included good ECOG performance status (0–2), normal lactate dehydrogenase (LDH), early stage disease (stage I–III), isolated extranodal organ involvement and later relapse (>100 days) post-HCT. Three year survival after HCT was significantly better in late than early relapse (53% (95% confidence interval (CI) [34–69%] vs. 36%, [20–52%], p=0.02). Of 72 relapsed patients, 29 (40%) survive at a median of 34 (3–148) months post transplant. The most common cause of death was underlying lymphoma (79%).
The overall prognosis of relapsed/progressive lymphoma after allogeneic HCT is disappointing, yet half of patients respond to withdrawal of immunosuppression and additional therapies. Novel treatments can control lymphoma with acceptable morbidity. Particularly for patients with later relapse, ongoing treatment after relapse can yield meaningful benefit and prolonged survival.
PMCID: PMC3132225  PMID: 21338707
Allogeneic hematopoietic cell transplantation; lymphoma; relapse
10.  Effect of Prophylactic Cyclosporine Therapy on ADAMTS13 Biomarkers in Patients with Idiopathic Thrombotic Thrombocytopenic Purpura 
American journal of hematology  2008;83(12):911-915.
Several reports have been published regarding the use of cyclosporine (CSA) in the treatment of idiopathic thrombotic thrombocytopenic purpura (TTP). We hypothesized that prophylactic CSA therapy may prevent recurrences in patients with a history of multiple relapses of TTP. Nineteen patients with idiopathic TTP were enrolled on prospective studies at Ohio State University between September 2003 and May 2007. Patients achieving remission remained on CSA therapy for 6 months, allowing us to evaluate the efficacy of CSA as prophylactic therapy. CSA was administered orally at a dose of 2–3 mg/kg in a twice a day divided dose in all patients and continued for a total of 6 months. Long-term clinical follow-up with serial analysis of ADAMTS13 biomarkers during and after CSA therapy were performed to evaluate the efficacy of CSA as a prophylactic therapy. 17/19(89%) patients completed 6 months of CSA therapy in a continuous remission. Two patients relapsed during therapy with CSA and 7 patients relapsed after discontinuing CSA therapy. Ten patients have maintained a continuous remission a median of 21 months (range, 5 to 46) after discontinuing CSA. The ADAMTS13 data suggest that CSA resulted in a significant increase in the ADAMTS13 activity during therapy with CSA. 8/9(89%) relapsing patients had severely deficient ADAMTS13 activity (< 5%) suggesting this is a significant risk factor for relapse of TTP. These data support the hypothesis that prophylactic CSA improves the ADAMTS13 activity and may be effective at preventing relapses in patients at risk for recurrences of TTP.
PMCID: PMC2824143  PMID: 18821711
thrombotic thrombocytopenic purpura; ADAMTS13; cyclosporine; relapse; prophylactic therapy
11.  Cyclosporine in Relapsed Subcutaneous Panniculitis-like T-Cell Lymphoma after Autologous Hematopoietic Stem Cell Transplantation 
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare T-cell lymphoma characterized by involvement of the subcutaneous tissue of neoplastic T lymphocytes. SPTCL with hemophagocytic syndrome (HPS) is associated with an aggressive clinical course and treatment of SPTCL with HPS is not well established. Cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) therapy is not successful in most patients suffering from SPTCL with HPS. The role of high dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) remains controversial. We report a case of relapsed SPTCL after CHOP chemotherapy and salvage chemotherapy followed by autologous HSCT, which had rapid improvement within weeks after cyclosporine and prednisolone. Immunosuppressive therapy may be an important and successful treatment option in SPTCL patients, even though they may have clinically aggressive disease.
PMCID: PMC3253869  PMID: 22247712
Panniculitis; Lymphoma; T-lymphocytes; Cyclosporine
12.  Cytophagic histiocytic panniculitis, hemophagocytic lymphohistiocytosis and undetermined autoimmune disorder: reconciling the puzzle 
Cytophagic histiocytic panniculitis is a rare disease, associated with either nonmalignant conditions or subcutaneous panniculitis-like T-cell lymphoma, and often also associated with hemophagocytic lymphohistiocytosis (HLH). We report the case of a 11-year-old boy with a history of secondary HLH who, after a local trauma, developed a painful, indurated plaque over the right thigh associated with relapsing HLH. Histopathologic findings from skin biopsy specimens revealed significant lobular panniculitis with benign histiocytes showing hemophagocytosis. High-dose intravenous methylprednisolone and cyclosporine A treatment was highly effective. A genetic study after a new, relapsing episode of HLH revealed an heterozygous missense mutation on STX 11 gene inherited from the mother.
PMCID: PMC3974103  PMID: 24524345
Panniculitis; Histiocytes; Hemophagocytosis
13.  Prolonged Cyclosporine Administration After Antithymocyte Globulin Delays But Does Not Prevent Relapse in Severe Aplastic Anemia 
American journal of hematology  2014;89(6):571-574.
In severe aplastic anemia, approximately one-third of responders to standard horse antithymocyte globulin (h-ATG) plus cyclosporine (CsA) will relapse. Anecdotal experience has suggested that a gradual CsA taper might avoid relapse, but this practice has not been rigorously assessed prospectively. In 2003, we adopted a strategy to taper CsA beyond 6 months, with the intention to reduce hematologic relapse compared to our extensive historical experience. In total, 102 patients received h-ATG/CsA for 6 months in two sequential clinical protocols: 67 patients (66%) responded and all had the CsA dose tapered per protocol over the subsequent 18 months (total of 2 years). The rate of relapse at 5 years was 33% (95% CI 27%-44%), which did not differ from our large historical relapse experience (patients treated before 2003) of 30-40%, in protocols in which CsA was simply discontinued at 6 months. However, time to relapse was prolonged by about 1 year with the longer CsA course. The rates of clonal evolution and overall survival did not differ between the two cohorts. We infer from this large prospective study that CsA taper as implemented delayed but did not prevent relapse. The kinetics of relapse with long course CsA does suggest that a lower long-term dose might be adequate to maintain patients in remission.
PMCID: PMC4074770  PMID: 24971433
14.  Extracorporeal Photophoresis 
Executive Summary
To assess the effectiveness, safety and cost-effectiveness of extracorporeal photophoresis (ECP) for the treatment of refractory erythrodermic cutaneous T cell lymphoma (CTCL) and refractory chronic graft versus host disease (cGvHD).
Cutaneous T Cell Lymphoma
Cutaneous T cell lymphoma (CTCL) is a general name for a group of skin affecting disorders caused by malignant white blood cells (T lymphocytes). Cutaneous T cell lymphoma is relatively uncommon and represents slightly more than 2% of all lymphomas in the United States. The most frequently diagnosed form of CTCL is mycosis fungoides (MF) and its leukemic variant Sezary syndrome (SS). The relative frequency and disease-specific 5-year survival of 1,905 primary cutaneous lymphomas classified according to the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification (Appendix 1). Mycosis fungoides had a frequency of 44% and a disease specific 5-year survival of 88%. Sezary syndrome had a frequency of 3% and a disease specific 5-year survival of 24%.
Cutaneous T cell lymphoma has an annual incidence of approximately 0.4 per 100,000 and it mainly occurs in the 5th to 6th decade of life, with a male/female ratio of 2:1. Mycosis fungoides is an indolent lymphoma with patients often having several years of eczematous or dermatitic skin lesions before the diagnosis is finally established. Mycosis fungoides commonly presents as chronic eczematous patches or plaques and can remain stable for many years. Early in the disease biopsies are often difficult to interpret and the diagnosis may only become apparent by observing the patient over time.
The clinical course of MF is unpredictable. Most patients will live normal lives and experience skin symptoms without serious complications. Approximately 10% of MF patients will experience progressive disease involving lymph nodes, peripheral blood, bone marrow and visceral organs. A particular syndrome in these patients involves erythroderma (intense and usually widespread reddening of the skin from dilation of blood vessels, often preceding or associated with exfoliation), and circulating tumour cells. This is known as SS. It has been estimated that approximately 5-10% of CTCL patients have SS. Patients with SS have a median survival of approximately 30 months.
Chronic Graft Versus Host Disease
Allogeneic hematopoietic cell transplantation (HCT) is a treatment used for a variety of malignant and nonmalignant disease of the bone marrow and immune system. The procedure is often associated with serious immunological complications, particularly graft versus host disease (GvHD). A chronic form of GvHD (cGvHD) afflicts many allogeneic HCT recipients, which results in dysfunction of numerous organ systems or even a profound state of immunodeficiency. Chronic GVHD is the most frequent cause of poor long-term outcome and quality of life after allogeneic HCT. The syndrome typically develops several months after transplantation, when the patient may no longer be under the direct care of the transplant team.
Approximately 50% of patients with cGvHD have limited disease and a good prognosis. Of the patients with extensive disease, approximately 60% will respond to treatment and eventually be able to discontinue immunosuppressive therapy. The remaining patients will develop opportunistic infection, or require prolonged treatment with immunosuppressive agents.
Chronic GvHD occurs in at least 30% to 50% of recipients of transplants from human leukocyte antigen matched siblings and at least 60% to 70% of recipients of transplants from unrelated donors. Risk factors include older age of patient or donor, higher degree of histoincompatibility, unrelated versus related donor, use of hematopoietic cells obtained from the blood rather than the marrow, and previous acute GvHD. Bhushan and Collins estimated that the incidence of severe cGvHD has probably increased in recent years because of the use of more unrelated transplants, donor leukocyte infusions, nonmyeloablative transplants and stem cells obtained from the blood rather than the marrow. The syndrome typically occurs 4 to 7 months after transplantation but may begin as early as 2 months or as late as 2 or more years after transplantation. Chronic GvHD may occur by itself, evolve from acute GvHD, or occur after resolution of acute GvHD.
The onset of the syndrome may be abrupt but is frequently insidious with manifestations evolving gradually for several weeks. The extent of involvement varies significantly from mild involvement limited to a few patches of skin to severe involvement of numerous organ systems and profound immunodeficiency. The most commonly involved tissues are the skin, liver, mouth, and eyes. Patients with limited disease have localized skin involvement, evidence of liver dysfunction, or both, whereas those with more involvement of the skin or involvement of other organs have extensive disease.
Cutaneous T Cell Lymphoma
The optimal management of MF is undetermined because of its low prevalence, and its highly variable natural history, with frequent spontaneous remissions and exacerbations and often prolonged survival.
Nonaggressive approaches to therapy are usually warranted with treatment aimed at improving symptoms and physical appearance while limiting toxicity. Given that multiple skin sites are usually involved, the initial treatment choices are usually topical or intralesional corticosteroids or phototherapy using psoralen (a compound found in plants which make the skin temporarily sensitive to ultraviolet A) (PUVA). PUVA is not curative and its influence on disease progression remains uncertain. Repeated courses are usually required which may lead to an increased risk of both melanoma and nonmelanoma skin cancer. For thicker plaques, particularly if localized, radiotherapy with superficial electrons is an option.
“Second line” therapy for early stage disease is often topical chemotherapy, radiotherapy or total skin electron beam radiation (TSEB).
Treatment of advanced stage (IIB-IV) MF usually consists of topical or systemic therapy in refractory or rapidly progressive SS.
Bone marrow transplantation and peripheral blood stem cell transplantation have been used to treat many malignant hematologic disorders (e.g., leukemias) that are refractory to conventional treatment. Reports on the use of these procedures for the treatment of CTCL are limited and mostly consist of case reports or small case series.
Chronic Graft Versus Host Disease
Patients who develop cGvHD require reinstitution of immunosuppressive medication (if already discontinued) or an increase in dosage and possibly addition of other agents. The current literature regarding cGvHD therapy is less than optimal and many recommendations about therapy are based on common practices that await definitive testing. Patients with disease that is extensive by definition but is indolent in clinical appearance may respond to prednisone. However, patients with more aggressive disease are treated with higher doses of corticosteroids and/or cyclosporine.
Numerous salvage therapies have been considered in patients with refractory cGvHD, including ECP. Due to uncertainty around salvage therapies, Bhushan and Collins suggested that ideally, patients with refractory cGvHD should be entered into clinical trials.
Two Ontario expert consultants jointly estimated that there may be approximately 30 new erythrodermic treatment resistant CTCL patients and 30 new treatment resistant cGvHD patients per year who are unresponsive to other forms of therapy and may be candidates for ECP.
Extracorporeal photopheresis is a procedure that was initially developed as a treatment for CTCL, particularly SS.
Current Technique
Extracorporeal photopheresis is an immunomodulatory technique based on pheresis of light sensitive cells. Whole blood is removed from patients followed by pheresis. Lymphocytes are separated by centrifugation to create a concentrated layer of white blood cells. The lymphocyte layer is treated with methoxsalen (a drug that sensitizes the lymphocytes to light) and exposed to UVA, following which the lymphocytes are returned to the patient. Red blood cells and plasma are returned to the patient between each cycle.
Photosensitization is achieved by administering methoxsalen to the patient orally 2 hours before the procedure, or by injecting methoxsalen directly ino the leucocyte rich fraction. The latter approach avoids potential side effects such as nausea, and provides a more consistent drug level within the machine.
In general, from the time the intravenous line is inserted until the white blood cells are returned to the patient takes approximately 2.5-3.5 hours.
For CTCL, the treatment schedule is generally 2 consecutive days every 4 weeks for a median of 6 months. For cGvHD, an expert in the field estimated that the treatment schedule would be 3 times a week for the 1st month, then 2 consecutive days every 2 weeks after that (i.e., 4 treatments a month) for a median of 6 to 9 months.
Regulatory Status
The UVAR XTS Photopheresis System is licensed by Health Canada as a Class 3 medical device (license # 7703) for the “palliative treatment of skin manifestations of CTCL.” It is not licensed for the treatment of cGvHD.
UVADEX (sterile solution methoxsalen) is not licensed by Health Canada, but can be used in Canada via the Special Access Program. (Personal communication, Therakos, February 16, 2006)
According to the manufacturer, the UVAR XTS photopheresis system licensed by Health Canada can also be used with oral methoxsalen. (Personal communication, Therakos, February 16, 2006) However, oral methoxsalen is associated with side effects, must be taken by the patient in advance of ECP, and has variable absorption in the gastrointestinal tract.
According to Health Canada, UVADEX is not approved for use in Canada. In addition, a review of the Product Monographs of the methoxsalen products that have been approved in Canada showed that none of them have been approved for oral administration in combination with the UVAR XTS photophoresis system for “the palliative treatment of the skin manifestations of cutaneous T-cell Lymphoma”.
In the United States, the UVAR XTS Photopheresis System is approved by the Food and Drug Administration (FDA) for “use in the ultraviolet-A (UVA) irradiation in the presence of the photoactive drug methoxsalen of extracorporeally circulating leukocyte-enriched blood in the palliative treatment of the skin manifestations of CTCL in persons who have not been responsive to other therapy.”
UVADEX is approved by the FDA for use in conjunction with UVR XTS photopheresis system for “use in the ultraviolet-A (UVA) irradiation in the presence of the photoactive drug methoxsalen of extracorporeally circulating leukocyte-enriched blood in the palliative treatment of the skin manifestations of CTCL in persons who have not been responsive to other therapy.”
The use of the UVAR XTS photopheresis system or UVADEX for cGvHD is an off-label use of a FDA approved device/drug.
Summary of Findings
The quality of the trials was examined.
As stated by the GRADE Working Group, the following definitions were used in grading the quality of the evidence.
Cutaneous T Cell Lymphoma
Overall, there is low-quality evidence that ECP improves response rates and survival in patients with refractory erythrodermic CTCL (Table 1).
Limitations in the literature related to ECP for the treatment of refractory erythrodermic CTCL include the following:
Different treatment regimens.
Variety of forms of CTCL (and not necessarily treatment resistant) - MF, erythrodermic MF, SS.
SS with peripheral blood involvement → role of T cell clonality reporting?
Case series (1 small crossover RCT with several limitations)
Small sample sizes.
Response criteria not clearly defined/consistent.
Unclear how concomitant therapy contributed to responses.
Variation in definitions of concomitant therapy
Comparison to historical controls.
Some patients were excluded from analysis because of progression of disease, toxicity and other reasons.
Unclear/strange statistics
Quality of life not reported as an outcome of interest.
The reported CR range is ~ 16% to 23% and the overall reported CR/PR range is ~ 33% to 80%.
The wide range in reported responses to ECP appears to be due to the variability of the patients treated and the way in which the data were presented and analyzed.
Many patients, in mostly retrospective case series, were concurrently on other therapies and were not assessed for comparability of diagnosis or disease stage (MF versus SS; erythrodermic versus not erythrodermic). Blood involvement in patients receiving ECP (e.g., T cell clonality) was not consistently reported, especially in earlier studies. The definitions of partial and complete response also are not standardized or consistent between studies.
Quality of life was reported in one study; however, the scale was developed by the authors and is not a standard validated scale.
Adverse events associated with ECP appear to be uncommon and most involve catheter related infections and hypotension caused by volume depletion.
GRADE Quality of Studies – Extracorporeal Photopheresis for Refractory Erythrodermic Cutaneous T-Cell Lymphoma
Chronic Graft-Versus-Host Disease
Overall, there is low-quality evidence that ECP improves response rates and survival in patients with refractory cGvHD (Table 2).
Patients in the studies had stem cell transplants due to a variety of hematological disorders (e.g., leukemias, aplastic anemia, thalassemia major, Hodgkin’s lymphoma, non Hodgkin’s lymphoma).
In 2001, The Blue Cross Blue Shield Technology Evaluation Centre concluded that ECP meets the TEC criteria as treatment of cGvHD that is refractory to established therapy.
The Catalan health technology assessment (also published in 2001) concluded that ECP is a new but experimental therapeutic alternative for the treatment of the erythrodermal phase of CTCL and cGvHD in allogenic HPTC and that this therapy should be evaluated in the framework of a RCT.
Quality of life (Lansky/Karnofsky play performance score) was reported in 1 study.
The patients in the studies were all refractory to steroids and other immunosuppressive agents, and these drugs were frequently continued concomitantly with ECP.
Criteria for assessment of organ improvement in cGvHD are variable, but PR was typically defined as >50% improvement from baseline parameters and CR as complete resolution of organ involvement.
Followup was variable and incomplete among the studies.
GRADE Quality of Studies – ECP for Refractory cGvHD
As per the GRADE Working Group, overall recommendations consider 4 main factors.
The tradeoffs, taking into account the estimated size of the effect for the main outcome, the confidence limits around those estimates and the relative value placed on the outcome.
The quality of the evidence (Tables 1 and 2).
Translation of the evidence into practice in a specific setting, taking into consideration important factors that could be expected to modify the size of the expected effects such as proximity to a hospital or availability of necessary expertise.
Uncertainty about the baseline risk for the population of interest.
The GRADE Working Group also recommends that incremental costs of healthcare alternatives should be considered explicitly alongside the expected health benefits and harms. Recommendations rely on judgments about the value of the incremental health benefits in relation to the incremental costs. The last column in Table 3 is the overall trade-off between benefits and harms and incorporates any risk/uncertainty.
For refractory erythrodermic CTCL, the overall GRADE and strength of the recommendation is “weak” – the quality of the evidence is “low” (uncertainties due to methodological limitations in the study design in terms of study quality and directness), and the corresponding risk/uncertainty is increased due to an annual budget impact of approximately $1.5M Cdn (based on 30 patients) while the cost-effectiveness of ECP is unknown and difficult to estimate considering that there are no high quality studies of effectiveness. The device is licensed by Health Canada, but the sterile solution of methoxsalen is not licensed.
With an annual budget impact of $1.5 M Cdn (based on 30 patients), and the current expenditure is $1.3M Cdn (for out of country for 7 patients), the potential cost savings based on 30 patients with refractory erythrodermic CTCL is about $3.8 M Cdn (annual).
For refractory cGvHD, the overall GRADE and strength of the recommendation is “weak” – the quality of the evidence is “low” (uncertainties due to methodological limitations in the study design in terms of study quality and directness), and the corresponding risk/uncertainty is increased due to a budget impact of approximately $1.5M Cdn while the cost-effectiveness of ECP is unknown and difficult to estimate considering that there are no high quality studies of effectiveness. Both the device and sterile solution are not licensed by Health Canada for the treatment of cGvHD.
If all the ECP procedures for patients with refractory erythrodermic CTCL and refractory cGvHD were performed in Ontario, the annual budget impact would be approximately $3M Cdn.
Overall GRADE and Strength of Recommendation (Including Uncertainty)
PMCID: PMC3379535  PMID: 23074497
15.  The Efficacy and Safety of Long-term Oral Cyclosporine Treatment for Patients with Atopic Dermatitis 
Annals of Dermatology  2010;22(1):9-15.
Steroids are used in conventional treatment of atopic dermatitis (AD) and they are very effective for improving the symptoms, but they also have several complications. Many studies have reported that short-term use of cyclosporine (CsA) is effective for severe AD as a substitute for steroid. However, there are very few studies on the long-term use of CsA for AD in the Korean population.
The purpose of this study was to investigate whether long-term CsA therapy is effective and safe for treating AD.
We performed a retrospective study of the patients with AD and who were treated with CsA at Kyung Hee Medical Center between January 2001 and February 2008. Among 147 patients, 61 received CsA treatment for more than 6 months. To evaluate the efficacy of CsA treatment, the objective SCORAD was checked for all 61 patients at every visit. Extensive laboratory tests were performed every two months to assess the safety of treatment.
The mean duration of CsA treatment was 13.5±8.4 months and the mean initial dose of CsA was 2.7±0.9 mg/kg/day. The mean objective SCORAD values significantly decreased from 34.1±11.2 at baseline to 11.4±10.7 after 6-month of CsA treatment (p<0.05). A significant decline of the SCORAD score was observed starting from 1-month of CsA treatment. The mean duration of remission was 4.5±2.9 months. A total of 13 adverse events in 10 patients were recorded during the study period. One patient dropped out due to renal dysfunction. Elevation of peripheral blood pressure was noted in 8 patients. Three patients complained of gastrointestinal troubles, and one patient had hypertrichosis, but the problems of these 4 patients were mild and easily treated.
We suggest that long-term, low-dose CsA treatment is safe and effective for patients who suffer from AD.
PMCID: PMC2883409  PMID: 20548874
Atopic dermatitis; Cyclosporine; Long-term treatment
16.  Treatment relapsed subcutaneous panniculitis-like T-cell lymphoma together HPS by Cyclosporin A 
Hematology Reports  2010;2(1):e9.
A 25-year-old man was diagnosised subcutaneous panniculitis-like T-cell lymphoma (SPTCL) through biopsy of a nodule from the anterior chest. After the treatment with prednisone 90 mg 3 weeks and tapered off in 1 month, the disease released, but relapsed together with symptions of hemophagocytic syndrome eight months after the termination of prednisone. CHOEP recipe was given but with unsatisfactory result until cyclosporine was prescribed. Cyclosporine was removed 6 months later. There is no evidence of clinical relapse 1 year later. This case suggest that cyclosporine could be a selectable treatment even in relapsed SPTCL.
PMCID: PMC3222267  PMID: 22184522
relapsed; subcutaneous panniculitis-like T-cell lymphoma; cyclosporin A.
17.  Rituximab retherapy in patients with relapsed aggressive B cell and mantle cell lymphoma 
Annals of Hematology  2009;89(3):283-289.
Neither effective salvage regimens nor the outcome and response to retherapy with rituximab containing chemotherapy have been defined for rituximab pre-treated patients with relapsing aggressive lymphoma. We report here a single-centre retrospective outcome analysis of second-line immunochemotherapy with rituximab. In 28 patients with relapsed or refractory diffuse large B cell lymphomas, first-line immunochemotherapy had induced objective responses in 18 patients. Nine of 28 patients responded to rituximab containing salvage therapy, leading to a median overall survival of 243 days after start of second immunochemotherapy. Long-term disease free survivors (1,260 and 949 days) were restricted to the group of twelve patients that had received allogeneic stem cell transplantation as consolidation therapy. In 21 patients with relapsed mantle cell lymphomas (MCL), 19 patients had reached remissions with first-line therapy. Of those, 16 patients experienced responses to salvage therapy with a median overall survival of 226 days. Noteworthy, none of patients with initial non-responding disease reached a remission with second immunochemotherapy. Seven patients with MCL stayed free from progression after high-dose therapy with autologous or allogeneic stem cell transplantation in two and five cases, respectively. In summary, responses to repeated immunotherapy with rituximab were observed in approximately one third and two thirds of initially responding patients with aggressive B cell lymphoma and mantle cell lymphoma, respectively, but not in primarily refractory disease. Lasting remissions were achieved only by high-dose chemotherapy with stem cell transplantation.
PMCID: PMC2808532  PMID: 19727725
Lymphoma; Relapse; Rituximab
18.  Bortezomib in multiple myeloma and lymphoma: a systematic review and clinical practice guideline 
Current Oncology  2006;13(5):160-172.
In patients with multiple myeloma, Waldenström macroglobulinemia, or lymphoma, what is the efficacy of bortezomib alone or in combination as measured by survival, quality of life, disease control (for example, time to progression), response duration, or response rate?
What is the toxicity associated with the use of bortezomib?
Which patients are more or less likely to benefit from treatment with bortezomib?
Evidence was selected and reviewed by two members of the Hematology Disease Site Group and by methodologists from the Program in Evidence-based Care (pebc) at Cancer Care Ontario. The practice guideline report was reviewed and approved by the Hematology Disease Site Group, which comprises hematologists, medical and radiation oncologists, and a patient representative. As part of an external review process, the report was disseminated to practitioners throughout Ontario to obtain their feedback.
Outcomes of interest were overall survival, quality of life, response rates and duration, and rates of adverse events.
A systematic search was conducted of the medline, embase, HealthStar, cinahl, and Cochrane Library databases for primary articles and practice guidelines. The resulting evidence informed the development of clinical practice recommendations. Those recommendations were appraised by a sample of practitioners in Ontario and modified in response to the feedback received. The systematic review and modified recommendations were approved by a review body w theithin pebc.
The literature review found one randomized controlled trial (rct)—the only published rct of bortezomib in relapsed myeloma. A number of phase ii studies were also retrieved, including a randomized phase ii study. No randomized trials were retrieved for lymphoma.
The rct found bortezomib to be superior to high-dose dexamethasone for median time to progression and 1-year survival in patients with relapsed myeloma, although grade 3 adverse events were more common in the bortezomib arm. Bortezomib is recommended as the preferred treatment option in patients with myeloma relapsing within 1 year of the conclusion of initial treatment; it may also be a reasonable option in patients relapsing at least 1 year after autologous stem-cell transplantation.
Practice Guideline
This evidence-based series applies to adult patients with myeloma, Waldenström macroglobulinemia, or lymphoma of any type, stage, histology, or performance status.
Based on the results of a large well-conducted rct, which represents the only published randomized study in relapsed myeloma, the Hematology Disease Site Group (dsg) offers the following recommendations:
For patients with myeloma refractory to or relapsing within 1 year of the conclusion of initial or subsequent treatment or treatments, including autologous stem-cell transplantation, and who are candidates for further chemotherapy, bortezomib is recommended as the preferred treatment option.
Bortezomib is also a reasonable option for patients relapsing at least 1 year after autologous stem-cell transplantation. The dsg is aware that thalidomide, alkylating agents, or repeat transplantation may also be options for these patients. However, evaluation of these other options is beyond the scope of this practice guideline.
For patients with myeloma relapsing at least 1 year after the conclusion of alkylating agent–based chemotherapy who are candidates for further chemotherapy, further treatment with alkylating agent–based chemotherapy is recommended.
Evidence is insufficient to support the use of bortezomib in patients with non-Hodgkin lymphoma or Waldenström macroglobulinemia outside of clinical trials.
Qualifying Statements
Limited evidence supports the appropriateness of a specific time-to-relapse period as being indicative of treatment-insensitive disease. The 1-year threshold provided in the foregoing recommendations is based on the opinion of the Hematology dsg.
For specific details related to the administration of bortezomib therapy, the dsg suggests that clinicians refer to the protocols used in major trials. Some of those details are provided here for informational purposes.
Bortezomib 1.3,g/m2 is given as a rapid intravenous bolus over 3–5 seconds on days 1, 4, 8, and 11 of a 21-day cycle; a minimum of 72 hours between doses is required to allow for recovery of normal proteasome function. Vital signs should be checked before and after each dose. A complete blood count is recommended before each dose, with blood chemistries (including electrolyte and creatinine levels) monitored at a minimum on days 1 and 8 of each cycle. The dose of bortezomib should be reduced or held immediately upon development of painful neuropathy, as described in the product monograph; dose modification may also be required for peripheral sensory neuropathy without pain or for other toxicities. Most toxicities are reversible if dose modification guidelines are followed.
Response to Treatment
Responses are usually apparent by 6 weeks (2 cycles). For patients achieving complete remission (determined by negative electrophoresis and immunofixation), bortezomib should be given for 2 additional cycles beyond the date of confirmed complete remission. In patients with progressive disease after 2 cycles or stable disease after 4 cycles, dexamethasone added to the bortezomib regimen (20 mg by mouth the day of and the day after each bortezomib dose) may produce an objective response. Bortezomib (with or without dexamethasone) should be continued in patients showing benefit from therapy (excluding those in complete remission) unless disease progression or significant toxicity is observed. Therapy should be discontinued in patients who do not respond to bortezomib alone if disease progression is seen within 2 cycles of the addition of dexamethasone.
The Hematology dsg recognizes that thalidomide is an active agent in multiple myeloma patients who have relapsed after autologous stem-cell transplantation or who are refractory to alkylating agent–based chemotherapy. To date, no reported rcts have evaluated thalidomide in this role, and specifically, no trials have compared thalidomide with bortezomib. Given these limitations, the members of the Hematology dsg regard thalidomide or bortezomib as therapy alternatives to dexamethasone.
PMCID: PMC3394599  PMID: 22792013
Bortezomib; Velcade; multiple myeloma; lymphoma; clinical practice guideline; systematic review
19.  Brentuximab Vedotin Treatment for Primary Refractory Hodgkin Lymphoma 
Case Reports in Hematology  2013;2013:351292.
Up to 40% of patients with advanced Hodgkin lymphoma (HL) become refractory or relapsed after current standard chemotherapy, among which primary refractory HL confers a particularly poor outcome. With intensive salvage chemotherapy and autologous stem cell transplantation, the long-term remission rate for these patients was only 30%, but more selective treatments with higher therapeutic index are needed. We report the experience of using a new anti-CD30 immunotoxin, brentuximab vedotin, in salvage treatment of a 30-year-old woman with primary refractory Hodgkin lymphoma. The patient presented with SVC syndrome due to the bulky mediastinal tumor and was confirmed to have classical Hodgkin lymphoma, nodular sclerosis type, stage IIIA. The tumor responded to induction chemotherapy transiently, but local progression was noted during subsequent cycles of treatment. Salvage radiotherapy to the mediastinal tumor, obtained no remission but was followed by rapid in-field progression and then lung metastasis. She declined stem cell transplantation and received salvage brentuximab vedotin (BV) therapy, which induced dramatic shrinkage of tumor without significant side effects. Serial followup of PET/CT imaging confirmed a rapid and continuous complete remission for 12 months. Although durability of the remission needs further observation, this case illustrates the excellent efficacy of brentuximab vedotin in primary refractory Hodgkin lymphoma.
PMCID: PMC3808109  PMID: 24198983
20.  Primary cutaneous γ/δ T-cell lymphoma. An atypical case with bone marrow granulomas 
Primary cutaneous γ/δ T-cell lymphoma is a rare variant of peripheral T-cell lymphoma which has been only recently set apart from subcutaneous panniculitis-like T-cell lymphoma and is known for its aggressive nature.
Main observation
We hereby report a case of primary cutaneous γ/δ T-cell lymphoma in a 35-year-old man with bone marrow granulomas, an unexpected feature in this lymphoma. The patient was treated with combination chemotherapy. Partial response was obtained, followed by relapse. Allogeneic stem cell transplantation was then carried out, and full remission was achieved.
Bone marrow granulomas can be an accompanying feature in primary cutaneous γ/δ T-cell lymphoma.
PMCID: PMC4410886  PMID: 25932058
bone; cutaneous gamma/delta T-cell lymphoma; lymphoma; subcutaneous panniculitis-like T-cell lymphoma; peripheral T-cell lymphoma; ulcer
21.  Cyclosporine A for the treatment of refractory nephrotic syndrome with renal dysfunction 
Cyclosporine A (CsA) is an immunosuppressant agent and is utilized as a second-line drug therapy for refractory nephrotic syndrome (RNS). In general, the use of CsA is strictly controlled in patients with an estimated glomerular filtration rate (eGFR) <30–40 ml/min/1.73 m2, and little is known about the safety and efficacy of CsA treatment in patients with RNS complicated by renal dysfunction. In the present study, the clinical data of 10 patients with RNS and renal dysfunction, who received CsA treatment between 2000 and 2009 in the Kidney Institute of PLA, were reviewed retrospectively. Pathologically, these patients included six cases with minimal change, two cases of diffuse mesangial proliferation and two cases of focal segmental glomerulosclerosis. Six months subsequent to the initiation of the CsA treatment, six patients achieved complete remission, two patients achieved remarkable remission and two patients achieved partial remission. Renal function was improved in all patients as represented by the improvement in the eGFR (28.6±3.8 ml/min/1.73 m2 prior to treatment versus 99.3±21.9 ml/min/1.73 m2 6 months subsequent to treatment). Few adverse CsA-related events were observed. These results suggest that renal dysfunction is not an absolute contraindication for CsA treatment in patients with RNS. The use of CsA is safe and efficacious and may, in certain cases, improve renal function in patients with RNS and renal impairment.
PMCID: PMC3881069  PMID: 24396423
cyclosporine A; refractory nephrotic syndrome; renal dysfunction; therapy
22.  Immunosuppressive Therapy in Patients with Aplastic Anemia: A Single-Center Retrospective Study 
PLoS ONE  2015;10(5):e0126925.
Aplastic anemia (AA) is a rare disease in which hematopoietic stem cells are severely diminished resulting in hypocellular bone marrow and pancytopenia. Etiology of AA includes auto immunity, toxins, infection, ionizing radiation, drugs and rare genetic disorders, but in the majority of cases no cause can be identified. In the present study we assessed response rate, survival, relapse and clonal evolution in patients with AA treated with immunosuppressive therapy.
Patients with AA who received immunosuppressive therapy between May 1998 and September 2013 were included in this study. Patients with non-severe AA (NSAA) were treated with cyclosporine (CsA) and danazol while patients with severe AA (SAA) as well as patients with NSAA who progressed to SAA after beginning of the treatment, were candidates for receiving antithymocyte globulin in addition to CsA and danazol.
Among the 63 studied patients, 29 (46%) had NSAA and 34 (54%) had SAA. Three months after treatment, overall response was 58.6% in NSAA and 12.9% in patients with SAA. Survival of all patients at 5, 10 and 15 years were 73%, 55% and 49%, respectively. Survival rates were significantly higher in patients with NSAA compared to patients with SAA as well as in patients who responded at 6 months compared to non-responders. The relapse risk was 39.7% at 10 years. Relapse occurred in patients who discontinued the therapy more than those who continued taking CsA (p value<0.01). The risk of clonal evolution was 9.9% at 10 years and 22.8% at 15 years after treatment.
This long-term retrospective study indicated that immunosuppressive therapy should be recommended to patients with AA. Also, our experience indicated that immunosuppressive therapy should not be discontinued after response to therapy in patients with both NSAA and SAA due to high risk of relapse. Low dose of CsA should be continued indefinitely.
PMCID: PMC4430492  PMID: 25970182
23.  Cyclosporin A and intravenous immunoglobulin treatment in polymyositis/dermatomyositis 
Objective: To describe the treatment of polymyositis (PM) and dermatomyositis (DM) with prednisone (PRED) and cyclosporin A (CSA) alone or associated with intravenous immunoglobulin (IVIg) and plasmapheresis (PEX).
Methods: Between 1992 and 1999 CSA and PRED were used to treat 20 patients with idiopathic myositis (12 with DM, eight with PM), diagnosed according to the Bohan and Peter criteria. In patients with refractory or relapsed disease, IVIg was added alone (seven cases) or synchronised with PEX (six cases). A standardised protocol was used to evaluate the patients, and assess disease activity and treatment response.
Results: Despite a transient response to PRED and CSA in 16/20 cases, this combination did not induce full remission in 13/20 cases, which led to the IVIg trial with or without PEX. Patients receiving PRED and CSA plus IVIg had a significantly higher probability of maintaining complete remission at the end of the four year follow up period than those treated with PRED and CSA alone (p<0.001). No further benefit was added by the PEX. The presence of arthritis significantly correlated with a poorer response to treatment (p<0.05). Adverse effects were gingival hyperplasia (one patient) and transient renal dysfunction (one).
Conclusions: This open study suggests that combined treatment with PRED, CSA, and IVIg is useful in patients with myositis, even those with refractory or relapsed disease; no increase in the number or type of side effects is seen.
PMCID: PMC1753869  PMID: 11779756
24.  Usefulness of F-18 FDG PET/CT in subcutaneous panniculitis-like T cell lymphoma: disease extent and treatment response evaluation 
Radiology and Oncology  2012;46(4):279-283.
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cutaneous lymphomas, accounting for less than 1% of cases of non-Hodgkin’s lymphoma. Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron-emission tomography/computed tomography (PET/CT) findings of SPTCL before and after treatment were rarely reported.
Case report.
We report a case of SPTCL in which F-18 FDG PET/CT showed increased FDG accumulations in numerous subcutaneous nodules without extracutaneous disease. Contrast-enhanced CT during F-18 FDG PET/CT showed multiple minimally enhancing nodules with an infiltrative pattern in the subcutaneous layer throughout the body. Follow-up F-18 FDG PET/CT after three cycles of CHOP chemotherapy showed a complete metabolic remission of the lesions.
F-18 FDG PET/CT is suggested to be useful in assessing the disease activity, extent and treatment response in SPTCL.
PMCID: PMC3572891  PMID: 23412422
subcutaneous panniculitis-like T-cell lymphoma; F-18 FDG; PET/CT
25.  Extranodal natural killer/T-cell lymphoma with long-term survival and repeated relapses: does it indicate the presence of indolent subtype? 
The Korean Journal of Hematology  2012;47(3):202-206.
Extranodal natural killer (NK)/T-cell lymphoma is a subtype of lymphoma that is derived from NK cells. It is considered as an aggressive form of non-Hodgkin's lymphoma because of frequent relapses and resistance to treatment. Relapsed NK/T-cell lymphoma often follows a fulminant course that is refractory to conventional chemotherapy treatment.
Several patients with extranodal NK/T-cell lymphoma showed long-term survival in spite of frequent relapses. Thus, the medical records of patients diagnosed with extranodal NK/T-cell lymphoma from 1995 to 2007 were reviewed and assessed.
Of the 140 cases reviewed, 6 were selected (4.29%). Each of these patients had a minimum of 3 relapses or disease progression during the follow-up period, and their median overall survival was 66 months (range, 42-89 months). They were grouped according to the atypical clinical behavior observed: (1) repeated relapses or progression (≥3 times) during follow-up; and (2) long-term survival of more than 40 months, as the longest overall survival median was previously considered at approximately 40 months. The clinicopathological and laboratory characteristics of these patients were similar to those of other extranodal NK/T-cell lymphoma patients. However, 5 of the studied cases involved relatively lower expression of the proliferation-related antigen Ki-67 (<40-50%), indicating less proliferative activity. Clinically, they showed delayed relapse for at least 20 months after the initial complete remission.
Our observations suggest that the clinical behavior of some extranodal NK/T-cell lymphoma patients differs from the typical clinical course.
PMCID: PMC3464337  PMID: 23071475
Extranodal NK/T-cell lymphoma; Relapse; Survival; Indolent

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