Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm arising from the antigen-presenting cells of the immune system. This disease usually involves the lymph nodes, and rarely, extranodal sites may be affected. The authors report a case of extranodal IDCS presenting in the pleura. A 32-yr-old man presented with progressive chest pain. Imaging studies showed diffuse pleural thickening with pleural effusion. Morphological and immunohistochemical analysis of an incisional biopsy of the pleura were consistent with a diagnosis of IDCS; tumor cells were positive for S100 and CD45, but negative for CD1a, CD21, CD35, B cell and T cell markers. The patient was administered chemotherapy, but died of progressive disease. Although its incidence is extremely rare, this case suggests that extranodal IDCS should be considered in the differential diagnosis of undifferentiated neoplasms and that immunohistochemical staining be performed using appropriate markers.
Dendritic Cell Sarcoma; Interdigitating; Pleura
Chemotherapy plus radiation treatment is effective in controlling
stage IA or IIA nonbulky Hodgkin’s lymphoma in 90% of patients but is
associated with late treatment-related deaths. Chemotherapy alone may
improve survival because it is associated with fewer late deaths.
We randomly assigned 405 patients with previously untreated stage IA
or IIA non-bulky Hodgkin’s lymphoma to treatment with doxorubicin,
bleomycin, vinblastine, and dacarbazine (ABVD) alone or to treatment with
subtotal nodal radiation therapy, with or without ABVD therapy. Patients in
the ABVD-only group, both those with a favorable risk profile and those with
an unfavorable risk profile, received four to six cycles of ABVD. Among
those assigned to subtotal nodal radiation therapy, patients who had a
favorable risk profile received subtotal nodal radiation therapy alone and
patients with an unfavorable risk profile received two cycles of ABVD plus
subtotal nodal radiation therapy. The primary end point was 12-year overall
The median length of follow-up was 11.3 years. At 12 years, the rate
of overall survival was 94% among those receiving ABVD alone, as compared
with 87% among those receiving subtotal nodal radiation therapy (hazard
ratio for death with ABVD alone, 0.50; 95% confidence interval [CI], 0.25 to
0.99; P = 0.04); the rates of freedom from disease progression were 87% and
92% in the two groups, respectively (hazard ratio for disease progression,
1.91; 95% CI, 0.99 to 3.69; P = 0.05); and the rates of event-free survival
were 85% and 80%, respectively (hazard ratio for event, 0.88; 95% CI, 0.54
to 1.43; P = 0.60). Among the patients randomly assigned to ABVD alone, 6
patients died from Hodgkin’s lymphoma or an early treatment
complication and 6 died from another cause; among those receiving radiation
therapy, 4 deaths were related to Hodgkin’s lymphoma or early toxic
effects from the treatment and 20 were related to another cause.
Among patients with Hodgkin’s lymphoma, ABVD therapy alone, as
compared with treatment that included subtotal nodal radiation therapy, was
associated with a higher rate of overall survival owing to a lower rate of
death from other causes. (Funded by the Canadian Cancer Society and the
National Cancer Institute; HD.6 ClinicalTrials.gov number, NCT00002561.)
A combination of Adriamycin (a.k.a. Doxorubicin), Bleomycin, Vinblastine, and Dacarbazine (ABVD) is the most commonly used chemotherapy regime for Hodgkin lymphoma. This highly effective treatment is associated with a significant risk of neutropenia. Various strategies are adopted to counter this commonly encountered problem, including dose modification, use of colony stimulating factors, and prophylactic or therapeutic use of antibiotics. Data to support these approaches is somewhat controversial, and in keeping with the paucity of definitive evidence, there is a wide disparity in the management of neutropenia in patients receiving ABVD chemotherapy. This paper summarizes the evidence for managing ABVD-related neutropenia during the treatment of Hodgkin lymphoma.
Interdigitating dendritic cell sarcoma (IDCS) is a very rare disease around the world and its prognosis is known to be aggressive. This reports a case diagnosed as IDCS of the axillary region treated in Soonchunhyang University Hospital. A 57-year-old female visited Soonchunhyang University Hospital with a left axillary mass. The mass was hard and fixed. Computed tomography observed a 7 cm lymph node at the left axilla, and core biopsy suspected sarcoma. In another study, there was no specific finding except the axillary lesion. Left axillary lymph node dissection (level I, II) was conducted and the pathologic report finally showed IDCS. The patient was treated with only radiotherapy and followed up without recurrence for 13 months up to now. IDCS is a very rare sarcoma that is hard to diagnose and progresses fast. Thus, treatment is very difficult. Proper treatment can be better established after more experiences.
Interdigitating dendritic cell sarcoma; Axilla
The mechanisms responsible for chemoresistance in patients with refractory classical Hodgkin lymphoma (CHL) are unknown. ATP-binding cassette (ABC) transporters confer multidrug resistance in various cancers and ABCC1 overexpression has been shown to contribute to drug resistance in the CHL cell line, KMH2.
We analyzed for expression of five ABC transporters ABCB1, ABCC1, ABCC2, ABCC3 and ABCG2 using immunohistochemistry in 103 pre-treatment tumor specimens obtained from patients with CHL. All patients received first-line standard chemotherapy with doxorubicin (Adriamycin®), bleomycin, vinblastine, and dacarbazine (ABVD) or equivalent regimens. ABCC1 was expressed in Hodgkin and Reed-Sternberg (HRS) cells in 16 of 82 cases (19.5%) and ABCG2 was expressed by HRS cells in 25 of 77 cases (32.5%). All tumors were negative for ABCB1, ABCC2 and ABCC3. ABCC1 expression was associated with refractory disease (p = 0.01) and was marginally associated with poorer failure-free survival (p = 0.06). Multivariate analysis after adjusting for hemoglobin and albumin levels and age showed that patients with CHL with HRS cells positive for ABCC1 had a higher risk of not responding to treatment (HR = 2.84, 95%, CI: 1.12-7.19 p = 0.028).
Expression of ABCC1 by HRS cells in CHL patients predicts a higher risk of treatment failure and is marginally associated with poorer failure-free survival using standard frontline chemotherapy regimens.
Classical Hodgkin lymphoma; ABCC1; ATP binding cassettes; Immunohistochemistry
Ovarian cryopreservation is a promising technique to preserve fertility in women with Hodgkin lymphoma (HL) treated with chemotherapy. Thus, the aim of this study was to examine harvested ovarian tissue for subclinical involvement by HL by morphology/immunohistochemistry, and to define patient and treatment factors predictive of oocyte yield. This was a retrospective analysis of 26 ovarian tissue samples harvested for cryopreservation from women with HL. Histology, immunohistochemistry and follicle density (number mm−3) was examined. Disease status and preharvest chemotherapy details were obtained on 24 patients. The median age was 22 years (range 13–29). Seven of 24 patients had infradiaphragmatic disease at time of harvest. Nine of 20 patients had received chemotherapy preharvest (ABVD (Adriamycin®, Bleomycin, Vinblastine and Dacarbazine)=7, other regimens=2). The seven receiving ABVD showed no difference in follicle density compared to patients not receiving treatment (n=14); (median=1555 vs 1620 mm3 P=0.97). Follicle density measurement showed no correlation with patient age (R2=0.0001, P=0.99). There was no evidence of HL involvement in the 26 samples examined (95% CI=0–11%). In conclusion, subclinical involvement of HL has not been identified in ovarian tissue, even when patients have infradiaphragmatic disease. Furthermore, the quality of tissue harvested does not appear to be adversely affected by patient's age or prior ABVD chemotherapy.
fertility; Hodgkin lymphoma; ovarian cryopreservation
To assess therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) risk in patients treated for Hodgkin lymphoma (HL) on successive generations of Stanford clinical trials.
Patients and Methods
Patients with HL treated at Stanford with at least 5 years of follow-up after completing therapy were identified from our database. Records were reviewed for outcome and development of t-AML/MDS.
Seven hundred fifty-four patients treated from 1974 to 2003 were identified. Therapy varied across studies. Radiotherapy evolved from extended fields (S and C studies) to involved fields (G studies). Primary chemotherapy was mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or procarbazine, mechlorethamine, and vinblastine (PAVe) in S studies; MOPP, PAVe, vinblastine, bleomycin, and methotrexate (VBM), or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in C studies; and VbM (reduced dose of bleomycin compared with VBM) or mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) in G studies. Cumulative exposure to alkylating agent (AA) was notably lower in the G studies compared with the S and C studies, with a 75% to 83% lower dose of nitrogen mustard in addition to omission of procarbazine and melphalan. Twenty-four (3.2%) of 754 patients developed t-AML/MDS, 15 after primary chemotherapy and nine after salvage chemotherapy for relapsed HL. The incidence of t-AML/MDS was significantly lower in the G studies (0.3%) compared with the S (5.7%) or C (5.2%) studies (P < .001). Additionally, in the G studies, no t-AML/MDS was noted after primary therapy, and the only patient who developed t-AML/MDS did so after second-line therapy.
Our data demonstrate the relationship between the cumulative AA dose and t-AML/MDS. Limiting the dose of AA and decreased need for secondary treatments have significantly reduced the incidence of t-AML/MDS, which was extremely rare in the G studies (Stanford V era).
Interdigitating dendritic cell sarcoma (IDCS) and histiocytic sarcoma (HS) are two distinct rare hematolymphoid neoplasms, and HS derived from a likely pre-existing IDCS has never been reported in the English literature. Diagnosis of such entities in excised specimens is difficult, but becomes more difficult with the scant amount of materials obtained with fine needle aspiration (FNA) and core needle biopsy. Here we present an interesting and unique case of an IDCS located within a mesenteric mass, which was initially diagnosed as IDCS from the cytology of FNA and core needle biopsy specimens. After brief chemotherapy, the patient again developed abdominal pain, and a HS was diagnosed based on the excised segmental small intestinal specimen. While the exact relationship between the IDCS and HS cannot be ascertained, it is most likely that the HS is derived from the IDCS, although co-existing HS in addition to IDCS from the cytology specimen cannot be completely ruled out.
Interdigitating dendritic cell sarcoma; histiocytic sarcoma; fine needle aspiration
The simultaneous presentation of the Hodgkin lymphoma and multiple myeloma in the absence of prior chemotherapy or radiation is very rare. Here, we discuss a 72-year-old patient who initially presented with generalized pruritis. Workup led to a diagnosis of multiple myeloma which progressed and required treatment. As part of his pretreatment workup, an MRI was performed to evaluate skeletal lesions. This revealed diffuse and bulky adenopathy which was confirmed by PET. A biopsy of an axillary node was consistent with the nodular sclerosing type Hodgkin lymphoma. He was treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy × 6 resulting in complete resolution of his adenopathy and pruritis as well as improvement in his myeloma.
In newly diagnosed patients with Hodgkin lymphoma (HL) the effect of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)-related neutropenia on chemotherapy delivery is poorly documented. The aim of this analysis was to assess the impact of chemotherapy-induced neutropenia (CIN) on ABVD chemotherapy delivery in HL patients.
Data from two similarly designed, prospective, observational studies conducted in the US and the EU were analysed. One hundred and fifteen HL patients who started a new course of ABVD during 2002-2005 were included. The primary objective was to document the effect of neutropenic complications on delivery of ABVD chemotherapy in HL patients. Secondary objectives were to investigate the incidence of CIN and febrile neutropenia (FN) and to compare US and EU practice with ABVD therapy in HL. Pooled data were analysed to explore univariate associations with neutropenic events.
Chemotherapy delivery was suboptimal (with a relative dose intensity ≤ 85%) in 18-22% of patients. The incidence of grade 4 CIN in cycles 1-4 was lower in US patients (US 24% vs. EU 32%). Patients in both the US and the EU experienced similar rates of FN across cycles 1-4 (US 12% vs. EU 11%). Use of primary colony-stimulating factor (CSF) prophylaxis and of any CSF was more common in the US than the EU (37% vs. 4% and 78% vs. 38%, respectively). The relative risk (RR) of dose delays was 1.54 (95% confidence interval [CI] 1.08-2.23, p = 0.036) for patients with vs. without grade 4 CIN and the RR of grade 4 CIN was 0.35 (95% CI 0.12-1.06, p = 0.046) for patients with vs. without primary CSF prophylaxis.
In this population of HL patients, CIN was frequent and FN occurrence clinically relevant. Chemotherapy delivery was suboptimal. CSF prophylaxis appeared to reduce CIN rates.
The management of classical Hodgkin's lymphoma (CHL) is a success story of modern multi-agent haemato-oncology. Prior to the middle of the twentieth century CHL was fatal in the majority of cases. Introduction of single agent radiotherapy (RT) demonstrated for the first time that these patients could be cured. Developments in chemotherapy including the mechlorethamine, vincristine, procarbazine and prednisolone (MOPP) and Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) regimens have resulted in cure rates of over 80%. Even in relapse, CHL patients can be salvaged with high dose chemotherapy and autologous haematopoietic stem cell transplantation (ASCT). Challenges remain, however, in finding new strategies to manage the small number of patients who continue to relapse or progress. In addition, the young age of many Hodgkin's patients forces difficult decisions in balancing the benefit of early disease control against the survival disadvantage of late toxicity. In this article we aim to summarise past trials, define the current standard of care and appraise future developments in the management of CHL.
Primary mediastinal choriocarcinoma is a rare extragonadal germ cell malignancy. We describe the first case of a patient who developed mediastinal choriocarcinoma after treatment for Hodgkin lymphoma (HL). A 25-year-old man with classic HL, nodular sclerosis subtype, underwent treatment with splenectomy followed by radiation therapy. Unfortunately, his disease relapsed with a paraspinal mass, and he was subsequently treated with MOPP (mechlorethamine, Oncovin, procarbazine, and prednisone) alternating with ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). He achieved a complete remission after 6 cycles. Ten years after treatment, the patient presented with a persistent cough, haemoptysis, right supraclavicular lymphadenopathy, and weight loss. His chest X-ray showed opacification of the lower right hemithorax with a widened mediastinum. Given unresponsiveness to several antibiotics and lack of evidence for lung volume loss, there were concerns over lung infiltration with relapsed lymphoma. Transbronchial fine needle aspiration biopsy suggested recurrence of his HL. MOPP alternating with ABVD was again given. Due to disease progression, brachytherapy as well as a cocktail of dexamethasone, cytarabine, and cisplatin were also tried. However, on a subsequent excisional lymph node biopsy, it turned out that the tumour was in fact choriocarcinoma and not relapsed HL. Unfortunately, despite aggressive therapy, the patient's disease rapidly progressed, and he died within 2 weeks.
Germ cell tumour; Choriocarcinoma; Hodgkin lymphoma; Mediastinal tumour
To examine ovarian reserve following chemotherapy in women with Hodgkin’s disease.
The study included nine patients who underwent ovarian tissue cryopreservation (OTCP) prior to chemotherapy consisting of the ABVD regimen (Adriamycin, bleomycin, vinblastine, and dacarbazine) and co-treatment with gonadotropin-releasing hormone agonist (GnRH-a) (Group A), and 13 patients treated by the ABVD protocol only without GnRH-a (Group B). The average age was 25.2 ± 2.7 years for the women in Group A and 31.8 ± 6.8 years for those in Group B.
Six months following the end of chemotherapy, the menstrual cycle resumed in all Group A patients and in four Group B patients who had amenorrhea. Eight Group B patients had regular menses during and after chemotherapy. None of the patients suffered from ovarian failure. Two Group A patients conceived in the first year after completing chemotherapy.
Co-treatment with GnRH-a has little effect on ovarian protection in women with Hodgkin’s disease.
Hodgkin’s disease; Chemotherapy; Ovarian tissue cryopreservation; GnRH-a; Ovarian reserve
Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare malignancy derived from professional antigen presenting cells. This report describes a case of IDCS arising in the salivary gland associated lymphoid tissue of the parotid gland of a 51 year woman, presenting with a painless neck swelling. Histologically, sheets of S100+/Ccd68+/CD45+/CD34−/CD1a− spindle cells were surrounded with an inflammatory infiltrate with no evidence of B or T cell clonal proliferations. No evidence of either human herpesvirus 8 or Epstein-Barr virus could be detected by quantitative polymerase chain reaction in the tumour cells with serological evidence of previous Epstein-Barr virus infection. The patient remains well and disease free 24 months after presentation without specific treatment.
interdigitating dendritic cell sarcoma; Kaposi’s sarcoma associated herpes virus; Epstein-Barr virus
Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm that mainly arises from the lymphoid tissues of the immune system. Although this neoplasm typically occurs anywhere along the lymph nodes, it can also be found at extranodal sites, especially in the head and neck. We experienced a rare case of extranodal IDCS in the nasal cavity, a location that has not been previously reported. A 73-year-old woman presented with a polyp-like mass in the nasal cavity and underwent endoscopic sinus surgery. A histologic study confirmed the mass as IDCS by immunohistochemistry with S-100 antibody, and postoperative adjuvant radiotherapy was administered. Although the incidence is extremely rare, this case suggests that extranodal IDCS should be considered in the differential diagnosis of nasal cavity masses.
Treatment of Hodgkin’s lymphoma (HL) is perceived to be relatively straightforward. Consequently, patients are not usually referred to hemato-oncologically specialized centres and are treated locally instead. Comprehensive findings beyond prospective controlled trials are therefore lacking. Clinical data of 209 patients who had received a HL diagnosis were collected. A total of 7 patients received radiotherapy (RT) alone (3%), 75 (35%) were treated with a combination of chemotherapy (CT) and RT and 127 patients received CT alone [mainly doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)]. Complete response (CR) following first-line treatment was achieved in 178 patients (85%) and in 195 (93%) after salvage treatment. Favorable disease (p=0.000359), limited-stage disease (p=0.0003), involvement of lymph nodes above the diaphragm (p=0.05) and absence of mediastinal bulky tumor involvement positively affected the CR rate following first-line treatment. Out of the 195 patients that achieved CR, 31 relapsed. Male gender (p=0.043) and age over 45 years (p=0.047) were significantly associated with an increased incidence of relapse. Age at diagnosis was the key factor affecting long-term outcome. The event-free survival (EFS) projected at 120 months was 80 and 57% for patients younger and older than 45 years, respectively (p=0.022). The overall survival (OS) projected at 120 months was 92 and 38% for patients younger and older than 45 years, respectively (p=0.00561). A second neoplasia was diagnosed in 8 patients. The development of a tumor in 4 cases (breast, lung and thyroid cancer) was likely RT-related. Only 1 patient not receiving RT developed acute myeloid leukemia. The EFS and OS of the 141 early-stage patients treated with CT + RT (n=62) or with CT alone (n=79) were not statistically different.
Hodgkin’s lymphoma; doxorubicin; bleomycin; vinblastine and dacarbazine; relapse; high-dose therapy
The metastatic propensity of invasive ductal carcinoma (IDC) of the breast correlates with axillary node involvement and with expression of the proliferation antigen Ki-67, whereas ductal carcinoma in situ (DCIS) is non-metastasising. To clarify whether concomitant DCIS affects IDC prognosis, we compared Ki-67 expression and node status of size-matched IDC subgroups either with DCIS (IDC-DCIS) or without DCIS (pure IDC).
We analysed data from 1355 breast cancer patients. End points were defined by the association of IDC (with or without DCIS) with grade, nodal status, Ki-67, and ER/HER2.
Size-matched IDC-DCIS was more likely than pure IDC to be screen detected (P=0.03), to occur in pre-menopausal women (P=0.002), and to be either ER-positive (P=0.002) or HER2-positive (P<0.0005), but less likely to be treated with breast-conserving surgery (P=0.004). Grade and Ki-67 were lower in IDC-DCIS than in pure IDC (P=0.02), and declined as the DCIS enlarged (P<0.01). Node involvement and lymphovascular invasion in IDC-DCIS increased with the size ratio of IDC to DCIS (P<0.01). A 60-month cancer-specific survival favoured IDC-DCIS over size-matched pure IDC (97.4 vs 96.0%).
IDC co-existing with DCIS is characterised by lower proliferation and metastatic potential than size-matched pure IDC, especially if the ratio of DCIS to IDC size is high. We submit that IDC-DCIS is biologically distinct from pure IDC, and propose an incremental molecular pathogenesis of IDC-DCIS evolution involving an intermediate DCIS precursor that remains dependent for replication on upstream mitogens.
breast neoplasms; pre-invasive; intraductal; Ki-67; carcinogenesis; tumour progression
Interdigitating dendritic cell sarcoma (IDCS) and retroperitoneal leiomyosarcoma are rare tumors. The optimal diagnosis, treatment and prognosis remain unknown. The current case report presents a 46-year-old male who exhibited with a left renal mass combined with a periprostatic mass. The patient underwent surgery twice, respectively for the resection of the two masses. The postoperative pathological examination confirmed the diagnosis of IDCS presenting in the kidney and retroperitoneal leiomyosarcoma in the pelvis. To the best of our knowledge, it is the first report of IDCS in the kidney and of the combined appearance of IDCS and retroperitoneal leiomyosarcoma in the same patient.
interdigitating dendritic cell sarcoma; leiomyosarcoma; diagnosis; therapy
Interdigitating Dendritic Cell Sarcoma (IDCS) is an infrequent dendritic cell tumor which mainly affects the lymphatic system. Intestinal metastasis from uterine IDCS is extremely rare. Here we report a case of a 76-year-old female presenting with vaginal bleeding and acute abdomen. The final diagnosis revealed a small bowel perforation due to metastatic involvement from uterine cervix IDCS. In this paper, we report the clinical manifestation, computed tomography and histopathological findings helpful for the accurate diagnosis of this rare tumor.
interdigitatin dendritic cell sarcoma; dendritic cell neoplasm; small intestine; uterine cervix.
Background. Hemophagocytic syndrome (HPS) is characterized by a hyperinflammatory reaction followed by alteration in cytotoxic function of Th1 lymphocytes and natural killer cells. We report a rare case of a patient that presented with fever and pancytopenia due to HPS associated with Hodgkin's lymphoma (HL). Case Report. A 69-year-old Caucasian woman was admitted presenting with complaints of fever, seizures, and low back pain that had lasted for two weeks. Laboratorial data showed pancytopenia. Bone marrow biopsy revealed infiltration by Reed-Sternberg cells and hemophagocytosis signs. Imaging studies showed mediastinal lymph nodes (stage IV B). She had been treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) followed by a good response. Conclusion. HPS associated with HL is a very rare and lethal disease, with mortality rates of about 15% to 60%. The prompt diagnosis of the underlying lymphoma may be an important strategy for optimizing the clinical approach and outcome.
The antibody-drug conjugate (ADC) cAC10-vcMMAE consists of the tubulin inhibitor monomethyl auristatin E (MMAE) conjugated to the chimeric anti-CD30 monoclonal antibody cAC10. This ADC potently interferes with the growth of CD30-positive haematological tumours, including Hodgkin lymphoma (HL) and anaplastic large-cell lymphoma. This study found improved antitumour activity in a preclinical model of HL when SGN-35 was combined with chemotherapeutic regimens such as ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or gemcitabine. Improved efficacy was also observed in high tumour burden models, indicating that combining ADCs with chemotherapeutic agents may be advantageous for the treatment of patients with relapsed or refractory HL.
SGN-35; antibody-drug conjugate; ABVD; gemcitabine; Hodgkin lymphoma
A small subset of patients with nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHLs) develop a non-Hodgkin lymphoma either concurrently or subsequently, usually T-cell/histiocyte-rich B-cell lymphomas (T/HRBCL), which are subtypes of diffuse large B-cell lymphomas (DLBCL). The standard treatment of DLBCL patients is rituximab-based chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisolone. However, the administration of this chemotherapy regimen to patients with DLBCL arising in NLPHL brings concern about the cardiac toxicity of anthracycline because the majority of these patients had already received anthracycline-based chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine at the time of NLPHL. Herein, we report 2 patients with sequential transformation of NLPHL to T/HRBCL. They initially presented with limited-stage NLPHL and subsequently developed T/HRBCL after 16 and 8 months, respectively. At the time of T/HRBCL, they were treated with rituximab, ifosfamide, carboplatin and etoposide, and complete responses were obtained.
Transformation; Nodular lymphocyte-predominant Hodgkin's lymphoma; T-cell/histiocyte-rich B-cell lymphoma; Chemotherapy
Although ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been established as the standard of care in patients with advanced Hodgkin lymphoma, newer regimens have been investigated, which have appeared superior in early phase II studies. Our aim was to determine if failure-free survival was superior in patients treated with the Stanford V regimen compared with ABVD.
Patients and Methods
The Eastern Cooperative Oncology Group, along with the Cancer and Leukemia Group B, the Southwest Oncology Group, and the Canadian NCIC Clinical Trials Group, conducted this randomized phase III trial in patients with advanced Hodgkin lymphoma. Stratification factors included extent of disease (localized v extensive) and International Prognostic Factors Project Score (0 to 2 v 3 to 7). The primary end point was failure-free survival (FFS), defined as the time from random assignment to progression, relapse, or death, whichever occurred first. Overall survival, a secondary end point, was measured from random assignment to death as a result of any cause. This design provided 87% power to detect a 33% reduction in FFS hazard rate, or a difference in 5-year FFS of 64% versus 74% at two-sided .05 significance level.
There was no significant difference in the overall response rate between the two arms, with complete remission and clinical complete remission rates of 73% for ABVD and 69% for Stanford V. At a median follow-up of 6.4 years, there was no difference in FFS: 74% for ABVD and 71% for Stanford V at 5 years (P = .32).
ABVD remains the standard of care for patients with advanced Hodgkin lymphoma.
Patients with Hodgkin lymphoma treated with DNA-breaking alkylating agents such as mechlorethamine and procarbazine in the MOPP regimen and with topoisomerase II inhibitors, such as etoposide did show a long-term risk of developing therapy-related myelodysplasia and acute myelogenous leukaemia (MDS/AML). With the introduction of the ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) regimen, this risk has substantially been reduced. In this review, different experiences are discussed to determine whether and how modifications of treatment in different cohorts of patients have reduced the overall risk of secondary MDS/AML. These data are drawn from large cohorts of patients treated over time with different therapies with an adequate follow-up.
Post-transplant lymphoproliferative disorders (PTLDs) are lymphoid or plasmacytic proliferations that develop as a consequence of immunosuppression in a recipient of a solid organ, bone marrow or stem cell allograft. The development of PTLDs is usually associated with Epstein-Barr virus (EBV) and the disorder is also termed EBV-associated lymphoproliferative disorder (LPD). The development of PTLD is a rare complication in autologous bone marrow/peripheral blood stem cell transplantation. In the present study, we report a case of EBV-associated LPD which developed following autologous peripheral blood stem cell transplantation for relapsing Hodgkin’s lymphoma. A 51-year-old male presented with swelling of the left cervical lymph nodes. A biopsy revealed nodular sclerosis classical Hodgkin’s lymphoma. Following four courses of ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) therapy, the Hodgkin’s lymphoma relapsed. CHASE (cyclophosphamide, etoposide, cytarabine, dexamethasone) therapy and autologous peripheral blood stem cell transplantation were performed. In the 128 days following the transplantation, lymph node swelling was noted and a biopsy specimen demonstrated EBV-associated LPD. The serum copy number of EBV-DNA was 2.7×103 copies/ml. The occurrence of EBV-associated LPD may be on the rise due to the increased number of patients undergoing immunosuppression therapy. The measurement of the serum EBV-DNA copy number and the detection of EBV-infected atypical lymphocytes using in situ hybridization are significant in establishing an early accurate diagnosis and initiating the correct treatment for EBV-associated LPD in patients with immunosuppression.
Epstein-Barr virus; lymphoproliferative disorder; Hodgkin’s lymphoma; autologous peripheral blood stem cell transplantation