Megumi Itabashi

Peripheral blood absolute lymphocyte/monocyte ratio as a useful prognostic factor in diffuse large B-cell lymphoma in the rituximab era

The tumor microenvironment, including tumor‐infiltrating lymphocytes and myeloid‐derived cells, is an important factor in the pathogenesis and clinical behavior of malignant lymphoma. However, the prognostic significance of peripheral lymphocytes and monocytes in lymphoma remains unclear.

European Treatment and Outcome Study score does not predict imatinib treatment response and outcome in chronic myeloid leukemia patients

The Sokal and Hasford scores were developed in the chemotherapy and interferon era and are widely used as prognostic indicators in patients with chronic myeloid leukemia (CML). Recently, a new European Treatment and Outcome Study (EUTOS) scoring system was developed. We performed a multicenter retrospective study to validate the effectiveness of each of the three scoring systems. The study cohort included 145 patients diagnosed with CML in chronic phase who were treated with imatinib. In the EUTOS low‐ and high‐risk groups, the cumulative incidence of complete cytogenetic response (CCyR) at 18 months was 86.9% and 87.5% (P = 0.797) and the 5‐year overall survival rate was 92.6% and 93.3% (P = 0.871), respectively. The cumulative incidence of CCyR at 12 months, 5‐year event‐free survival and 5‐year progression‐free survival were not predicted using the EUTOS scoring system. However, there were significant differences in both the Sokal score and Hasford score risk groups. In our retrospective validation study, the EUTOS score did not predict the prognosis of patients with CML in chronic phase treated with imatinib.

Serum ferritin level is a prognostic marker in patients with peripheral T-cell lymphoma

The prognostic value of serum ferritin level in patients with peripheral T‐cell lymphoma (PTCL) remains unknown.

Cytomegalovirus Pneumonia after Anti-CC-chemokine Receptor 4 Monoclonal Antibody (Mogamulizumab) Therapy in an Angioimmunoblastic T-cell Lymphoma Patient.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive T-cell lymphoma. A 63-year-old man was diagnosed with AITL. He received 6 cycles of CHOP therapy, but showed progressive disease. Subsequently, he received ESHAP chemotherapy; however, it was not effective. He received mogamulizumab (an anti-CCR4 monoclonal antibody). After 4 cycles, his respiratory condition worsened and he was diagnosed with cytomegalovirus (CMV) pneumonia. Despite antiviral and antibiotic therapy, he died. We speculate that the combination of progressive lymphoma with mogamulizumab and chemotherapy likely caused CMV pneumonia. Because mogamulizumab therapy causes immunosuppression, if CMV pneumonia is suspected, then rapid treatment should be initiated.

Hyper-recovery of platelets after induction therapy is a predictor of relapse-free survival in acute myeloid leukemia.

Abstract We verified the association between standard clinical and laboratory variables and the risk of relapse in acute myeloid leukemia (AML), which led us to retrospectively examine the effect of regeneration of hematopoiesis in patients with newly diagnosed AML. We used data from 230 patients who obtained remission after cytarabine-based induction chemotherapy. Platelet counts ≥500 × 109/L and hemoglobin levels ≥9 g/dL on day 28 after treatment initiation were significantly associated with relapse-free survival (RFS) rate, conferring respective multivariate risk ratios of 0.38 (95% CI: 0.18–0.79) and 0.60 (95% CI: 0.40–0.89) for the occurrence of relapse or death. No disease relapse occurred in core binding factor leukemia patients whose platelet counts recovered ≥500 × 109/L at 28 days after therapy initiation. We conclude that regeneration of hematopoiesis, especially platelet hyper-recovery, after induction chemotherapy is a significant predictor of RFS in patients with AML.

Intestinal amoebiasis in a patient with acute graft‐versus‐host disease after allogeneic bone marrow transplantation successfully treated by metronidazole

Amoebiasis has rarely been reported in patients undergoing hematopoietic stem cell transplantation, although it is a world‐wide infection and extremely common. We present a case of intestinal amoebiasis unexpectedly revealed by colonoscopy after allogeneic bone marrow transplantation from a human leukocyte antigen‐mismatched unrelated donor for acute myeloid leukemia arising from chronic myelomonocytic leukemia and successfully treated by metronidazole.

Analysis of outcomes in patients with supra-diaphragmatic vs infra-diaphragmatic diffuse large B cell lymphoma treated with R-CHOP therapy.

The prognostic implications of infra-diaphragmatic (InD) versus supra-diaphragmatic (SpD) primary lesions in limited-stage diffuse large B-cell lymphoma (DLBCL) remains unknown. This retrospective study aimed to assess the prognostic impact of spD and InD lesions as well as presence of gastrointestinal (GI) involvements in adults with limited-stage DLBCL. We analyzed data from 178 patients with limited-stage DLBCL who were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy at 7 institutions of the Yokohama City University Hematology Group between 2003 and 2009. The median age was 63 years (range, 18-80 years). The primary sites were SpD in 109 patients, and InD in 69. No statistical differences in progression-free survival (PFS) or overall survival (OS) were observed between patients with SpD lesions and those with InD lesions. However, when patients with SpD lesions, InD lesions with (n=35), and without (n=34) GI involvement were compared, the presence of GI lesions was associated with favorable PFS. The multivariate analysis revealed that SpD or InD localization had no independent effect on PFS or OS, whereas the presence of GI lesions was correlated with favorable PFS (P=0.024, HR 0.09).

Emergence of del(20q) in a patient in molecular remission of chronic myelogenous leukemia during imatinib treatment, with reduction following imatinib discontinuation

Chronic myelogeneous leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the BCR-ABL1 fusion gene, which is usually the result of the t(9;22)(q34;q11.2) translocation known as the Philadelphia chromosome (Ph) [1–3]. Current first-line therapy for CML includes tyrosine kinase inhibitors (TKIs), such as the firstgeneration TKI imatinib. Treatment with imatinib achieves high rates of cytogenetic response and major molecular response (MMR) [4–6]. Jabbour et al. [7] reported that 9% of patients with newly diagnosed CML in the chronic phase developed chromosomal abnormalities in Ph-negative metaphases during imatinib therapy. In that study, 1% of the cohort developed del(20q), but the details were unclear [7]. Here, we present an imatinib-treated patient in remission from CML who developed a cytogenetic abnormality, del(20q), in Ph-negative clones that disappeared after discontinuation of imatinib. A 29-year-old Japanese woman was referred to our department in January 2012 because of leukocytosis and thrombocytosis, which was found while she underwent examination for gastrointestinal bleeding. Peripheral blood counts showed the following: hemoglobin, 12.7 g/dL; platelets, 785  109/L, and white blood cells, 17  109/L, with 1% myelocytes, 1% metamyelocytes, 57.5% segmented neutrophils, 14% lymphocytes, 2% monocytes, 11.5% eosinophils, and 13% basophils. No organomegaly was observed. Sokal score was 0.62, and she belonged to the low risk group. The bone marrow showed marked hypercellularity with myeloid hyperplasia without an increase in blast percentage. Cytogenetic analysis of bone marrow cells at diagnosis showed 46,XX,t(9;22)(q34;q11.2) in 19/20 and 46,XX in 1/20 metaphases analyzed. Fluorescence in situ hybridization (FISH) analysis of cells in interphase was performed to detect the BCR-ABL1 fusion gene. Consequently, a BCR-ABL1 fusion signal was detected in 99/100 cells analyzed. RT-PCR analysis of bone marrow cells using primers for the majorbcr rearrangement provided 4.8  104 copies/mg RNA. Therefore, the patient was diagnosed with CML in the chronic phase. In January 2012, treatment was initiated with imatinib at 400 mg/day. Complete hematologic response (CHR) was achieved after 3 weeks, complete cytogenetic response (CCyR) after 3 months, MMR after 6 months, and molecularly undetectable leukemia (MUL) after 1 year. MUL was defined as MR4.0, 4.0 log reduction, in this case. Two years after initiating imatinib therapy, bone marrow analysis was performed, demonstrating normocellularity without dysplasia. Cytogenetic analysis showed 46,XX,del(20)(q1?) in 4/20 and 46,XX in 16/20 metaphases analyzed. FISH analysis detected del(20q) in 6/100 cells analyzed. RT-PCR analysis could not detect major-bcr-abl rearrangement, indicating that MUL was maintained. After 30 months of treatment with imatinib, cytogenetic analysis showed 47,XX, 22 in 1/20, 47,XX, mar in 1/20, and 46,XX in 18/20 metaphases. FISH analysis detected del(20q) in 1/100 cells analyzed. After 33 months of treatment, the dosage of imatinib was reduced to 300 mg/day because of grade 2 neutropenia. In January 2014, after 36 months of treatment with imatinib, neutropenia had resolved, and cytogenetic analysis showed 46,XX,del(20)(q1?) in 11/20 and 46,XX in 9/20 metaphases. FISH analysis detected del(20q) in 53/100 cells analyzed. Major-bcr-abl was not detected by RT-PCR analysis. At that time, the bone marrow showed hypocellularity but no evidence of dysplasia, such as myelodysplastic syndrome (MDS). We were concerned that the chromosomal abnormalities may increase and lead to MDS. We also hypothesised that the patient could sustain MUL after imatinib withdrawal, as she had rapidly achieved MUL and maintained this for over 2 years [8]. Therefore, imatinib treatment was stopped Leukemia & Lymphoma, 2016; 57(1): 201–202 January

Allogeneic Hematopoietic Stem Cell Transplantation after Conditioning Regimens with Fludarabine/melphalan or Fludarabine/busulfan for Patients with Hematological Malignancies: A Single-center Analysis

Objective Fludarabine plus melphalan (FM) and fludarabine plus busulfan (FB) are two major conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods We retrospectively analyzed patients who underwent allo-HSCT after a conditioning regimen consisting of FM or FB with/without total body irradiation for hematological malignancies between 2005 and 2014. Results There were 41 patients who met the criteria. The median follow-up time for the survivors was 3 years. Thirty-two patients received allo-HSCT after the FM regimen and nine patients received allo-HSCT after the FB regimen. Patients who received FB were older than those who received FM (p=0.041). There was no significant difference in the 3-year overall survival between patients who had received FB and those who had received FM (29.6% vs. 56.5%, p=0.267). The 3-year cumulative incidence of relapse was significantly higher in patients who had received FB than that in patients who had received FM (66.7% vs. 17.8%, p=0.004), and FB was an independent prognostic factor for relapse by a multivariate analysis (hazard ratio, 9.8; 95% confidential interval, 2.5-39.3; p=0.001). When we restricted the evaluation to patients with acute myeloid leukemia and myelodysplastic syndrome, the 3-year cumulative incidence of relapse was also significantly higher in patients who had received FB than that in patients who had received FM (75.0% vs. 16.1%, p=0.004). Conclusion The results suggest that FM may provide better disease control than FB.

Favorable prognosis in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia patients following hematopoietic stem cell transplantation

The prognosis for adult patients with acute lymphoblastic leukemia (ALL) is poor. Standard risk subsets of ALL patients have a survival rate of about 50% that can further reduce to <10% in those with Philadelphia chromosome-positive (Ph+) ALL (1, 2). However, tyrosine kinase inhibitors (TKI) have remarkably improved outcomes in patients with Ph+ ALL (3). Here, we compare the outcomes of newly diagnosed adult Ph+ ALL and Ph-negative (Ph ) B-cell ALL (B-ALL) cases. We retrospectively analyzed 35 consecutive, newly diagnosed cases of B-ALL admitted to our center between January 2003 and September 2014, who were treated with standard induction chemotherapy. Imatinib was administered to patients with Ph+ ALL. Thirty-five patients were included (males, 18; females, 17; Ph+ ALL, 14; Ph B-ALL, 21; median age, 41 yr; range, 16–64 yr). The complete remission rate (CRR) for the first induction therapy for Ph+ ALL and Ph ALL was 100% and 90%, respectively. The five-yr overall survival (5yOS) of Ph+ ALL and Ph ALL patients was 64% and 63%, respectively (p = 0.45). The five-yr progression free survival (5yPFS) for Ph+ ALL and Ph ALL patients was 85% and 62%, respectively (p = 0.30). Next, we analyzed 24 patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT; Ph+ ALL,12; Ph ALL, 12). Patient characteristics of the patients are shown in Table 1. The 5yOS following HSCT of Ph+ ALL and Ph ALL patients was 71% and 38%, respectively (p = 0.13). The 5yPFS after HSCT of Ph+ ALL and Ph ALL patients was 72% and 33%, respectively (p = 0.04). The five-yr cumulative incidence of relapse after HSCT for Ph+ ALL and Ph ALL patients was 8% and 50%, respectively (p = 0.03). We consider two main reasons for the improved prognosis of patients with Ph+ ALL. First, TKIs have aided most patients with Ph+ ALL in achieving complete remission (3). The CRR for the first induction therapy for Ph+ ALL patients was 100% in our study. Second, the survival rate of non-myeloablative HSCT has increased in the elderly (4). Although one-third of patients with Ph+ ALL received non-myeloablative HSCT, the HSCT outcome was not as low as that in other high-risk ALL, one-fifth of whom received non-myeloablative HSCT. Conversely, the prognosis of the other high-risk ALL in this study was lower than that reported elsewhere (4, 5). One potential