Comparison of Prognostic Indices in Japanese Patients with Diffuse Large B-cell Lymphoma in the Yonago Area.

BACKGROUND: Several prognostic indices for diffuse large B-cell lymphoma (DLBCL) have been developed. Which index is appropriate for Japanese patients with DLBCL treated in real-world practice is unknown. METHODS: The prognostic performances of the original international prognostic index (IPI), age-adjusted IPI, National Comprehensive Cancer Network-IPI, elderly IPI and revised IPI were compared using patients with DLBCL treated in a single institute in the Yonago area in Japan. RESULTS: From 2005 through 2015, 182 patients with de novo DLBCL were treated with chemotherapy in Tottori University Hospital; 154 (85%) patients received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) although full dose was administered in 63 (35%) patients. The median age of the patients was 71 years (range 18 to 91). Three-year overall survival rate was 71.8% (95% CI, 64.1% to 78.2%). All indices significantly discriminate risk groups for overall survival of the patients (P < 0.001). Although no statistical difference of performance was found among these indices, the best scores of model fit/discrimination measures were beaten out by age-adjusted IPI, the simplest and three-factor model. CONCLUSION: Age-adjusted IPI is still usable in real-world practice while a better predictive model is desired for Japanese patients with DLBCL.

Analysis of Acute Transfusion Reactions and Their Occurrence Times.

Acute transfusion reactions (ATRs) are significantly relevant to the morbidity and mortality of patients. ATRs are mostly not severe and rarely cause severe conditions, including anaphylactic shock. The aim of this study was to clarify the frequency of ATRs and the time of event occurrence. A total of 18,745 transfusions were administered to 11,718 patients during a 3-year period. Adverse reactions including at least one sign or symptom were collected through a report system in 143 of 2,478 (5.7%) platelet concentrate transfusions, 105 of 6,629 (1.6%) red blood cell component transfusions and 51 of 2,307 (2.2%) fresh frozen plasma transfusions. Allergic signs and symptoms accounted for 70% of all adverse events. Severe signs and symptoms were observed in 7.1% of patients. These events appeared significantly earlier than those of non-severe signs and symptoms (median time 20 min vs 100 min, P < 0.05). For patients who have had repetitive transfusion-associated adverse events, preventive treatments for adverse events should be proactively promoted.

Efficacy of bendamustine on thrombocytopenia and hemolytic anemia secondary to CD5-positive B-cell lymphoma with massive splenomegaly in a patient with rheumatoid arthritis.

Chemotherapy for lymphoma may be avoided in the presence of coincident cytopenia. In case of immune cytopenia secondary to lymphoma, treatment of cytopenia is the same for primary cases, however, chemotherapy for lymphoma may be effective at the cost of severe hematological toxicity. The present study reports a complex case of thrombocytopenia and direct antiglobulin test-negative hemolytic anemia, thus mimicking Evans syndrome, secondary to cluster of differentiation 5-positive B-cell lymphoma with massive splenomegaly, in a patient suffering from rheumatoid arthritis for two decades. Treatment with prednisolone, high-dose dexamethasone, eltrombopag and rituximab for cytopenia were not effective. Chemotherapy with bendamustine subsequently resolved the cytopenia, additionally resulting in a complete remission of lymphoma. Thus, bendamustine may have a role in the management of lymphoma complicated with severe cytopenia.

Acute undifferentiated leukemia (stem cell acute leukemia) showing differentiation to Langerhans cell-like cells in lymph nodes.

A 75-year-old woman was referred to our hospital with suspected leukemia. Complete blood count demonstrated WBC 3,810/µl with 26% blasts, Hb of 11.7 g/dl and Plt of 18.0×104/µl. Bone marrow aspiration revealed blasts (86.3%) with expressions of CD34, CD7, TdT, CD33, and CD117. MPO was negative. Chromosomal analysis of the bone marrow showed isolated trisomy 10 in all leukemic cells (20/20). Swelling of superficial lymph nodes was also observed. Cervical lymph node biopsy revealed leukemic blasts which had the same phenotype as those in the bone marrow except that proliferation of Langerhans cell-like cells (LCs) was observed in the paracortex. LCs had pale cytoplasm and grooved nuclei, and were positive for both CD1a and S100 protein. Trisomy 10 was detected in both the leukemic blasts and the LCs by fluorescence in situ hybridization. This rare case strongly suggests leukemic cells to differentiate into LCs.

CD5-negative mantle cell lymphoma resembling extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue : a case report.

A 71-year-old male underwent an upper gastrointestinal endoscopy ; as a result of a biopsy, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) was suspected. Abdominal computed tomography scan disclosed an approximately 4-cm-large mass in the ileocecal region. After ileocecal resection, the patient was diagnosed with MALT lymphoma (CD79a(+), CD20(+), CD3(-), CD5(-), CD10(-), and cyclin D1(-)). He achieved complete remission after receiving chemotherapy. However, four years after the primary onset, he was diagnosed with recurrence. Although he achieved remission again by salvage therapy, six years after the primary onset, he was referred to our hospital with second recurrence. Colonoscopy revealed the appearance of multiple lymphomatous polyposis and biopsy specimens showed monotonous proliferation of centrocyte-like cells (CD79a(+), CD20(+), CD3(-), CD5(-), CD10(-), and cyclin D1(+)), which were consistent with mantle cell lymphoma (MCL) except for CD5. The result of reactivity to cyclin D1 was different from that at initial diagnosis, so we reexamined the initial surgical specimens, the histological and histochemical features of which were proven to be the same as those of colonic biopsy specimens. Finally, the patient was diagnosed with CD5-negative MCL (marginal zone-like variant). As MALT lymphoma and MCL sometimes show similar histological features, they are difficult to distinguish from each other. It is necessary to take the possibility of this rare phenotype of MCL into consideration and to reexamine the initial diagnosis, especially if the clinical course is unusual for MALT lymphoma. This case is very interesting in view of its indolent clinical feature and phenotype.

Phase I/II study of tandem high-dose chemotherapy with autologous peripheral blood stem cell transplantation for advanced multiple myeloma.

The efficacy and safety of high-dose chemotherapy with tandem autologous peripheral blood stem cell transplantation (auto-PBSCT) were evaluated in a multicenter clinical study of patients with advanced multiple myeloma. Eligible patients (n = 40) were consecutively enrolled in the phase I/II study and received 2-4 cycles of vincristine-adriamycin-dexamethasone regimen. The responding patients underwent PBSC harvesting following high-dose cyclophosphamide and filgrastim administration. The first auto-PBSCT (n = 32) following high-dose melphalan (200 mg/m(2)) was performed within 2 months of PBSC harvesting; the second auto-PBSCT (n = 28) was scheduled 3-6 months later. Treatment-related mortality was 2.5% (n = 1) throughout the protocol. Grade 4 nonhematologic toxicity occurred in 12.5 and 14.3% of the first and second auto-PBSCT patients, respectively. All but one patient (who died) achieved hematopoietic recovery. For the 28 patients completing the second auto-PBSCT, the results were favorable with a response rate of 65% (complete response rate = 27.5%, n = 11); the five-year progression-free survival and overall survival were 20.3 and 66.5%, respectively. In conclusion, high-dose chemotherapy with tandem auto-PBSCT is feasible and safe with a favorable response rate in treating advanced multiple myeloma in Japan.

Complete remission from chronic myelogenous leukemia--blastic crisis caused by reduced intensity stem cell transplantation following partial remission due to imatinib.

We report a 55-year-old man who showed no change after chemotherapy for chronic myelogenous leukemia-blastic crisis (CML-BC) in 1998. Allo-peripheral blood stem cell transplantation (PBSCT) was then performed and Complete remission (CR) was achieved, but recurrence was seen in 2001. Imatinib administration brought about partial remission (PR) and then a reduced intensity stem cell transplantation (RIST) was performed. The bcr-abl gene disappeared and Ph1 chromosome disappearance was ascertained. CR was thus achieved. There are still no established radical methods of treating CML-BC. Thus, therapy by allograft after the patient has entered hematological remission with imatinib is considered a new way of dealing with cases of CML-BC.

A possible role for the loss of CD27-CD70 interaction in myelomagenesis.

CD27 is a marker of memory B cells and its interaction with its ligand, CD70, is very important for differentiation into plasma cells. Although CD27 is detected on normal plasma cells, its expression is significantly reduced with the progression of multiple myeloma (MM), including monoclonal gammopathy of undetermined significance (MGUS). CD27+ myeloma cells are thought to represent an early phase of myeloma, as CD27+ plasma cells from MM patients were found to be composed of normal plasma cells (CD19+/CD38++) and myeloma cells (CD19-/CD38++), and monoclonality was detected in the CD27+/CD38++ fraction. Given that the lack of CD27 on plasma cells is related to myelomagenesis and that the pro-apoptotic protein Siva is thought to bind to the cytoplasmic tail of CD27, we analysed alterations of cell growth and genes caused by co-culturing CD27-transfected myeloma cell lines (U266, KMS-5) with CD70-transfected NIH3T3 cells. CD27-CD70 interaction could not induce apoptosis in either type of myeloma transfectant, and binding between Siva and CD27 was not detected. cDNA microarray (human apoptosis CHIP) analysis showed a significant upregulation of expression of the ectodermal neural cortex 1 (ENC1) gene by CD27-CD70 interaction compared with CD27 transfection alone. These findings show that the relationship between the loss of CD27 and oncogenesis of plasma cells is not simple. It remains unclear whether the lack of CD27 leads to evasion of apoptosis.

[A patient with mantle cell lymphoma who successfully underwent auto-PBSCT in combination with in vivo purging of tumor cells using rituximab].

The chimeric anti-CD20 monoclonal antibody rituximab was recently approved for the treatment of malignant B cell lymphoma. We report the case of a 49 year-old female with advanced mantle cell lymphoma (MCL), who successfully underwent auto-peripheral blood stem cell transplant (auto-PBSCT) in combination with in vivo purging of tumor cells using rituximab. Systemic swelling was detected in her lymph nodes, and she was histologically diagnosed with MCL. From bone marrow involvement and 28% of lymphoma cells in her peripheral blood, she was identified as stage IV of MCL. She achieved a partial response (PR) after three cycles of standard chemotherapy (ProMACE-CytaBOM) followed by 1 course of rituximab at 375 mg/m2 per week for four weeks. Prior to treatment with rituximab, IgH/bcl-1 translocation in her peripheral blood was found to be positive in 0.5% of 199 cells. After administration of rituximab, this fell to 0% in her peripheral blood and bone marrow. Stem cells were mobilized with cyclophosphamide at 2,000 mg/m2 for 2 days, followed by granulocyte colony-stimulating factor (G-CSF). On one day prior to harvest, rituximab was infused at 375 mg/m2 for in vivo purging of tumor cells. The IgH/bcl-1 translocation in the peripheral blood stem cell harvest (PBSCH) product was found to be 0%. Subsequently, a pretreatment regimen of CBDCA at 350 mg/m2 x 4, ETP at 500 mg/m2 x 3, MCNU at 200 mg/m2 x 1, and CPA at 2,000 mg/m2 x 2 was adopted to condition the transplant, followed by auto-PBSCT. After the transplant, the patient achieved an uncertain complete response (CRu). The present case suggests in vivo purging with rituximab is effective, and that this method may have a role as a first-line therapy in MCL patients who respond poorly to standard treatment.