Maximum standardized uptake value (SUVmax) and maximum tumor diameter (MTD) have been shown to reflect survival outcome in diffuse large B cell lymphoma (DLBCL). However, applying these values to primary extranodal DLBCL is difficult because they are separate nosological entities with differences in genetic origin. We therefore decided to evaluate whether SUVmax and MTD on 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18-FDG) positron emission tomography (PET) would affect the survival outcome in primary extranodal DLBCL.
From October 2005 to November 2010, 76 primary extranodal DLBCL patients receiving R-CHOP therapy were analyzed. All patients had undergone an initial 18-FDG PET/CT and conventional computed tomography (CT) of the neck, chest, abdomen, and pelvis for staging. Median follow-up period was 35 months.
The SUVmax and MTD cut-off values were 11.0 and 7.5 cm, respectively. SUVmax≥11.0 predicted a short progression free survival (PFS, P=0.002) and overall survival (OS, P=0.002). MTD≥7.5 cm was associated with poor PFS (P=0.003) and OS (P=0.003). High International Prognostic Index (IPI) was also associated with the survival outcome (PFS, P=0.046; OS, P=0.030). Multivariate analysis revealed that SUVmax≥11.0 (PFS, hazard ratio [HR]=10.813, P=0.024; OS, HR=6.312, P=0.015); MTD≥7.5 cm (PFS, HR=5.631, P=0.008; OS, HR=4.072, P=0.008); and high IPI (PFS, P=0.027; OS, P=0.046) were independent prognostic factors.
It appears that both MTD and SUVmax can be independent prognostic factors in primary extranodal DLBCL.
Lymphoma; Large B-cell; Extranodal
This study evaluates the effectiveness of immunochemotherapy and radiation therapy in the treatment of patients with primary bone lymphoma (PBL).
We retrospectively reviewed the medical records of 33 patients with PBL who were treated at 6 medical centers in Korea from 1992 to 2010. Clinicopathological features and treatment outcomes were analyzed.
The median age of the patients participating in our study was 40 years. The most common sites of involvement were the pelvis (12.36%) and femur (11.33%). CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens were administered to 20 patients (61%), and R-CHOP (rituximab plus CHOP) was administered to the remaining 13 patients (39%). The overall response rate was 89% (complete response, 76%; partial response, 12%). The overall survival (OS) of patients with solitary bone lesions was longer than that of patients with multiple bone lesions (median OS: not reached vs. 166 months, respectively; P=0.089). Addition of rituximab to CHOP did not significantly affect either OS or progression-free survival (P=0.53 and P=0.23, respectively). Combining radiation therapy with chemotherapy also did not improve the OS or progression-free survival of patients with solitary bone lesions.
Conventional cytotoxic chemotherapy remains an effective treatment option for patients with PBL. Additional benefits of supplementing chemotherapy with either rituximab or radiation therapy were not observed in this study. Further investigation is needed to characterize the role of immunochemotherapy in treating patients with PBL.
Bone lymphoma; Radiotherapy; Rituximab
Granulocyte-colony stimulating factor (G-CSF) is extensively used to improve neutrophil count during anti-cancer chemotherapy. We investigated the effects of G-CSF on several leukemic cell lines and screened for the expression of the G-CSF receptor (G-CSFR) in various malignant cells.
We examined the effects of the most commonly used commercial forms of G-CSF (glycosylated lenograstim and nonglycosylated filgrastim) on various leukemic cell lines by flow cytometry. Moreover, we screened for the expression of G-CSFR mRNA in 38 solid tumor cell lines by using real-time PCR.
G-CSF stimulated proliferation (40-80% increase in proliferation in treated cells as compared to that in control cells) in 3 leukemic cell lines and induced differentiation of AML1/ETO+ leukemic cells. Among the 38 solid tumor cell lines, 5 cell lines (hepatoblastoma, 2 breast carcinoma, squamous cell carcinoma of the larynx, and melanoma cell lines) showed G-CSFR mRNA expression.
The results of the present study show that therapeutic G-CSF might stimulate the proliferation and differentiation of malignant cells with G-CSFR expression, suggesting that prescreening for G-CSFR expression in primary tumor cells may be necessary before using G-CSF for treatment.
G-CSF; Differentiation; Proliferation; Solid tumor; AML
Radioiodine is regularly used in the treatment of thyroid cancer to eliminate residual malignant tissue after thyroidectomy and to treat metastasis. Because of the low dose of radioiodine used to treat thyroid cancer patients, leukemia is an uncommon complication of exposure to radioiodine. Here, we present a patient who developed therapy-related acute myeloid leukemia with inv(16)(p13.1q22);CBFβ-MYH11, eosinophilia, and K-ras mutation and who had been treated with very low-dose radioiodine following total thyroidectomy.
Radioiodine; Thyroid cancer; Acute myeloid leukemia; CBFβ-MYH11; Eosinophilia; K-ras
A 23-year-old male presented with pulmonary tuberculosis and swelling of both lower limbs. He was put on antitubercular treatment. Hemogram showed mild anemia and Pseudo Pelger-huet cells. The bone marrow (BM) examination showed 52% promyelocytes with regular round to oval nuclei, few granules and were positive for CD13 and CD33, and negative for HLA-DR. Cytogenetic analysis of the BM aspirate revealed an apparently balanced t(11;17)(q23;q21). Final diagnosis rendered was acute promyelocytic leukemia (APL) with t(11;17)(q23;q21); ZBTB16/RARA. APL is a distinct subtype of acute myeloid leukemia. The variant APL with t(11;17)(q23;q21) cases that are associated with the ZBTB16/RARA fusion gene have been reported as being resistant to all-trans-retinoic acid (ATRA). Therefore, differential diagnosis of variant APL with t(11;17)(q23;q12) from classical APL with t(15;17)(q22;q12); PML-RARA is very important. Here we have discussed the importance of distinct morphology of variant APL and also significance of rare presentation with tuberculosis.
ZBTB16-RARα variant; Tuberculosis; Promyelocytes
We describe 2 cases in which radiographic evidence of thromboembolic events was obtained during germ cell tumor diagnosis. There was no evidence of coagulation factor abnormalities or contributory procedures or drugs in either patient. We used anticoagulation therapy for thrombolysis in one patient, but in the other, the thromboembolism resolved spontaneously.
Thromboembolism; Germ cell tumor; Chemotherapy
Arsenic trioxide (As2O3) is a well-known and effective treatment that can result in clinical remission for patients diagnosed with acute promyelocytic leukemia (APL). The biologic efficacy of As2O3 in APL and solid tumor cells has been explained through its actions on anti-proliferation, anti-angiogenesis, and apoptotic signaling pathways. We theorize that As2O3 activates a pathway that disrupts microtubule dynamics forming abnormal, nonfunctioning mitotic spindles, thus preventing cellular division. In this study, we investigated how As2O3 induces apoptosis by causing microtubule dysfunction.
Cultured NB4 cells were treated with As2O3, paclitaxel, and vincristine. Flow cytometric analysis was then performed. An MTT assay was used to determine drug-mediated cytotoxicity. For tubulin polymerization assay, each polymerized or soluble tubulin was measured. Microtubule assembly-disassembly was measured using a tubulin polymerization kit. Cellular microtubules were also observed with fluorescence microscopy.
As2O3 treatment disrupted tubulin assembly resulting in dysfunctional microtubules that cause death in APL cells. As2O3 markedly enhanced the amount of depolymerized microtubules. The number of microtubule posttranslational modifications on an individual tubulin decreased with As2O3 concentration. Immunocytochemistry revealed changes in the cellular microtubule network and formation of polymerized microtubules in As2O3-treated cells.
The microtubules alterations found with As2O3 treatment suggest that As2O3 increases the depolymerized forms of tubulin in cells and that this is potentially due to arsenite's negative effects on spindle dynamics.
Acute promyelocytic leukemia; Arsenic trioxide; Tubulin; Apoptosis; Antimitotic agents
Knowledge of the roles of tacrolimus and minidose methotrexate (MTX) in the prevention of acute graft-versus-host disease (aGVHD) in pediatric allogeneic hematopoietic stem cell transplantation (HSCT) is limited. We retrospectively evaluated the engraftment status, incidence of aGVHD and chronic GVHD (cGVHD), and toxicities of tacrolimus and minidose MTX in aGVHD prophylaxis in children undergoing allogeneic HSCT.
Seventeen children, who underwent allogeneic HSCT and received tacrolimus and minidose MTX as GVHD prophylaxis from March 2003 to February 2011, were reviewed retrospectively. All the patients received tacrolimus since the day before transplantation at a dose of 0.03 mg/kg/day and MTX at a dose of 5 mg/m2 on days 1, 3, 6, and 11.
Of the 17 patients, 9 received human leukocyte antigen (HLA)-matched related donor transplants, and 8 received HLA-matched, or partially mismatched unrelated donor transplants. The median time for follow-up was 55 months. The incidence of aGVHD in the related and unrelated donor groups was 22.2% and 42.9%, respectively. cGVHD was not observed. To maintain therapeutic blood levels of tacrolimus, the younger group (<8 years of age) required an increased mean dose compared to the older group (≥8 years) (P=0.0075). The adverse events commonly associated with tacrolimus included hypomagnesemia (88%), nephrotoxicity (23%), and hyperglycemia (23%).
Tacrolimus and minidose MTX were well tolerated and effective in GVHD prophylaxis in pediatric patients undergoing allogeneic HSCT. Children <8 years of age undergoing HSCT required increased doses of tacrolimus to achieve therapeutic levels.
Tacrolimus; Methotrexate; Allogeneic hematopoietic stem cell transplantation; Acute graft-versus-host disease; Children
Radioimmunotherapy agents have a highly significant role in autologous stem cell transplantation as they improve tolerability and increase the efficacy of the conditioning regimen.
We retrospectively analyzed the efficacy and toxicity of yttrium-90 ibritumomab tiuxetan (Zevalin) combined with intravenous busulfan, cyclophosphamide, and etoposide (Z-BuCyE) compared with those of BuCyE alone followed by autologous stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). The efficacy, toxicity, and engraftment characteristics were compared between 19 patients who received Z-BuCyE and 19 historical controls who received BuCyE.
The 2 treatment groups shared similar baseline characteristics. The median time to platelet engraftment (>20×109/L) and neutrophil engraftment (>0.5×109/L) did not significantly differ between the Z-BuCyE group (12 days and 10 days, respectively) and the BuCyE group (12 days and 10 days, respectively). No significant differences were observed between the groups with respect to toxicities and treatment-related mortality. The median follow-up period was 30.4 months, and median event-free survival was generally better in the Z-BuCyE group (12.5 months) vs. the BuCyE group (6.2 months, P=0.236). No significant difference in overall survival between the groups was noted.
Adding ibritumomab tiuxetan to BuCyE high-dose chemotherapy may benefit patients with relapsed or refractory B-cell NHL with no risk of additional toxicity.
Yttrium-90 ibritumomab tiuxetan; BuCyE; Autologous stem cell transplantation; Non-Hodgkin lymphoma
The criteria by Camitta for diagnosis in severe aplastic anemia (SAA) has been used since 1976. However, there has been no attempt to verify the Camitta's criteria, that the survival in patients with SAA may differ by absolute neutrophil count (ANC), platelet count (PLT), and corrected reticulocyte count (CRC), which are components of the Camitta's criteria.
117 SAA patients diagnosed by the Camitta's criteria were analyzed, retrospectively. Univariate and multivariate analyses were used to evaluate the factors affecting overall survival (OS).
Response by immunosuppressive therapy (IST) or stem cell transplantation (SCT) significantly affected OS (P=0.001). Therefore, we excluded treatment responders for analysis. Finally, 92 SAA patients including treatment non-responders by IST or SCT and conservative care group were analyzed by using univariate and multivariate analyses. The median age of analyzed patients was 54.5 years. Male to female ratio was 1:1. The median follow-up duration was 74.23 months (range, 54.71-93.74 months). The median ANC, PLT, and CRC were 394/µL, 12,000/µL, and 0.39%, respectively. In multivariate analyses, ANC <500/µL or ≥500/µL (P=0.015, HR 2.694, 95% CI: 1.20-6.01) and age (P=0.015, HR 1.022, 95% CI: 1.00-1.04) were the significant factors for OS.
ANC could be an essential, not an optional criterion for diagnosing SAA. This study suggests the possibility that the Camitta's criteria be modified. Studies in large cohorts are needed to transform the Camitta's criteria.
Camitta's criteria; Severe aplastic anemia; Absolute neutrophil count
Diamond Blackfan anemia (DBA), characterized by impaired red cell production, is a rare condition that is usually symptomatic in early infancy. The purpose of this study was to assess nationwide experiences of DBA encountered over a period of 20 years.
The medical records of 56 patients diagnosed with DBA were retrospectively reviewed from November 1984 to July 2010. Fifteen institutions, including 13 university hospitals, participated in this study.
The male-to-female ratio of patients with DBA was 1.67:1. The median age of diagnosis was 4 months, and 74.1% were diagnosed before 1 year of age. From 2000 to 2009, annual incidence was 6.6 cases per million. Excluding growth retardation, 38.2% showed congenital defects: thumb deformities, ptosis, coarctation of aorta, ventricular septal defect, strabismus, etc. The mean hemoglobin concentration was 5.1±1.9 g/dL, mean corpuscular volume was 93.4±11.6 fL, and mean number of reticulocytes was 19,700/mm3. The mean cellularity of bone marrow was 75%, with myeloid:erythroid ratio of 20.4:1. After remission, 48.9% of patients did not need further steroids. Five patients with DBA who received hematopoietic transplantation have survived. Cancer developed in 2 cases (3.6%).
The incidence of DBA is similar to data already published, but our study had a male predilection. Although all patients responded to initial treatment with steroids, about half needed further steroids after remission. It is necessary to collect further data, including information regarding management pathways, from nationwide DBA registries, along with data on molecular analyses.
Diamond Blackfan anemia; Anemia; Congenital defects
The objective of this study was to determine if there are differences in common red blood cell (RBC) indices and platelet concentrations during pregnancy and to establish if any observed differences in these parameters were based on the patient's ethnicity.
From an electronic perinatal database which stores laboratory and clinical information on a large number of births at a regional hospital specializing in obstetrical care, RBC index and platelet concentration data were retrospectively analyzed at various time points throughout pregnancy. RBC index data was collected from 8,277 pregnant women (5,802 Caucasian pregnant women and 2,475 non-Caucasian pregnant women). Platelet concentration data was available from 8252 pregnant women (5,784 Caucasian pregnant women and 2,468 non-Caucasian pregnant women).
Hemoglobin (HGB) levels were significantly higher amongst Caucasian women compared to non-Caucasian women (P at least <0.01) starting at 27 weeks gestation and proceeding until term. There was no significant difference in the mean PLT counts between Caucasian and non-Caucasian pregnant women at any point during gestation.
There are ethnic differences in HGB levels, but not the platelet concentrations, during pregnancy. Based on this finding it would be reasonable to conduct formal prospective studies to determine the clinical significance of this difference and to establish the threshold for diagnosing gestational anemia, especially in pregnant non-Caucasian women.
Anemia; Complete blood count; Hemoglobin; Pregnancy; Reference Ranges
Chronic graft versus host disease (GVHD) is a frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT), but simultaneous small bowel obstruction is rare. Here, we report a child with acute myeloid leukemia who received an allogeneic HSCT from an unrelated matched donor. After HSCT, the patient developed severe chronic GVHD involving the small intestine, leading to obstruction of the terminal ileum. Small bowel resection was performed, and the symptoms improved without severe complications. Bowel obstruction should be considered as a possible complication of chronic GVHD; surgery may be a valuable corrective measure.
Acute myeloid leukemia; Hematopoietic stem cell transplantation; Graft versus host disease; Intestinal obstruction
Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a distinctive lymphoma characterized by an infiltration of subcutaneous tissue by neoplastic cytotoxic T cells. There was no distinction between TCR alpha/beta phenotype and TCR gamma/delta phenotype, and anthracycline-based chemotherapy was usually used for both. Here, we report a patient with recurrent SPTL who achieved a second long-term complete remission by repeated cyclosporine A (CsA) treatment. From 2000 to 2001, the patient received anthracycline-based combination chemotherapy. However, the treatment did not induce long-term remission. In 2002, he received cyclosporine treatment for about 6 months. This resulted in a 5-year remission that ended in relapse in 2008. He received CsA treatment once again and attained a second long-term remission. This case suggests that re-treatment with CsA can be a good option for relapsed SPTL cases and can result in long-term remission.
Subcutaneous panniculitis-like T-cell lymphoma; Cyclosporine; Treatment outcome
Interdigitating dendritic cell sarcoma (IDCS) is a very rare and aggressive neoplasm that arises from antigen presenting cells. IDCS usually involves lymph nodes; however, extra-nodal involvement has also been reported. Because a consistent standard therapy for IDCS has not been established to date, we report a case of the successful treatment of disseminated IDCS using ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine). A 64-year-old man was diagnosed with IDCS on the basis of immunohistochemical findings of a biopsy specimen of the inferior nasal concha. Immunohistochemical staining showed a positive reaction for CD68, leukocyte common antigen, and S-100 protein, but a negative reaction for CD34, CD1a, and CD21. Imaging studies showed cervical and axillary lymphadenopathies, subcutaneous nodules, and a soft tissue lesion in the nasal cavity. Treatment with the ABVD regimen resulted in complete remission after 8 cycles of chemotherapy.
IDCS; ABVD chemotherapy; Complete remission
Malignant lymphoma encompasses a wide variety of distinct disease entities. It is generally more common in developed countries and less common in developing countries. The East Asia region has one of the lowest incidence rates of malignant lymphoma. The incidence of malignant lymphoma around the world has been increasing at a rate of 3-4% over the last 4 decades, while some stabilization has been observed in developed countries in recent years. The reasons behind this lymphoma epidemic are poorly understood, although improving diagnostic accuracy, the recent AIDS epidemic, an aging world population and the increasing adoption of cancer-causing behaviors are suggested as contributing factors. Etiologies of malignant lymphoma include infectious agents, immunodeficiency, autoimmune disease, exposure to certain organic chemicals, and pharmaceuticals. The distribution of many subtypes exhibit marked geographic variations. Compared to the West, T/natural killer (NK) cell lymphomas (T/NK-cell lymphoma) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are relatively more common, whereas other B-cell lymphomas, particularly follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, are less common in Asia. Some subtypes of T/NK-cell lymphomas defined by Epstein-Barr virus association are predominantly Asian diseases, if not exclusively so. Both ethnic and environmental factors play roles in such diversity. In this review, we discuss the geographic distribution and etiology of malignant lymphoma, as well as the trend.
Malignant lymphoma; Epidemiology; Asia
Cellular therapy with dendritic cells (DCs) is emerging as a useful immunotherapeutic tool to treat multiple myeloma (MM). DC-based idiotype vaccination was recently suggested to induce idiotype-specific immune responses in MM patients. However, the clinical results so far have been largely disappointing, and the clinical effectiveness of such vaccinations in MM still needs to be demonstrated. DC-based therapies against MM may need to be boosted with other sources of tumor-associated antigens, and potent DCs should be recruited to increase the effectiveness of treatment. DCs with both high migratory capacity and high cytokine production are very important for effective DC-based cancer vaccination in order to induce high numbers of Th1-type CD4+ T cells and CD8+ cytotoxic T lymphocytes. The tumor microenvironment is also important in the regulation of tumor cell growth, proliferation, and the development of therapeutic resistance after treatment. In this review, we discuss how the efficacy of DC vaccination in MM can be improved. In addition, novel treatment strategies that target not only myeloma cells but also the tumor microenvironment are urgently needed to improve treatment outcomes.
Cellular immunotherapy; Dendritic cell; Multiple myeloma; Cytotoxic T lymphocyte; Immune response