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Objectives: Patients with myeloproliferative neoplasms (MPNs) are at higher risk of developing secondary malignancies. In this study, we focused on patients with MPNs that complicated lymphoid neoplasms. To analyze the real-world status of lymphoid neoplasm treatment in patients with pre-existing MPNs in Japan, we conducted a multicenter retrospective study., Methods: Questionnaires were sent to collect the data on patients who were first diagnosed with either polycythemia vera, essential thrombocythemia or myelofibrosis and who later were complicated with lymphoid neoplasms defined as malignant lymphoma, multiple myeloma, or chronic lymphocytic leukemia/small cell lymphoma., Results: Twenty-four patients with MPNs complicated by lymphoid neoplasms were enrolled (polycythemia vera, n  = 8; essential thrombocythemia, n  = 14; and primary myelofibrosis, n  = 2). Among these, diffuse large B-cell lymphoma (DLBCL) was the most frequently observed ( n  = 13, 54.1%). Twelve (92.3%) of the patients with DLBCL received conventional chemotherapy. Among these 12 patients, regarding cytoreductive therapy for MPNs, 8 patients stopped treatment, one continued treatment, and two received a reduced dose. Consequently, most patients were able to receive conventional chemotherapy for DLBCL with a slightly higher dose of granulocyte colony-stimulating factor support than usual without worse outcomes. All 3 patients with multiple myeloma received a standard dose of chemotherapy., Conclusion: Our data indicate that if aggressive lymphoid neoplasms develop during the course of treatment in patients with MPNs, it is acceptable to prioritize chemotherapy for lymphoma.

We present the case of a patient with aplastic anemia (AA) who was treated with eltrombopag. To the best of our knowledge, this is the first report of the disappearance of monosomy 7 after eltrombopag treatment. The patient was a 77-year-old woman with intraoral hematoma and purpura who was diagnosed with very severe AA with a normal karyotype. After combination therapy with rabbit antithymocyte globulin, cyclosporin, and granulocyte-colony-stimulating factor (G-CSF), pancytopenia transiently improved. When pancytopenia worsened again, the patient was administered darbepoetin alfa for renal anemia and danazol. Bone marrow examination showed 2.5% blasts with the karyotype 45,XX,-7[17]/46,XX[3], and 87.0% of marrow cells had monosomy 7, as determined by 7q31 interphase fluorescence in situ hybridization (FISH) analysis. Pancytopenia was considered owing to the evolution of myelodysplastic syndrome, and we stopped G-CSF and darbepoetin treatment. As she refused treatment with a hypomethylating agent, considering her age, eltrombopag was started against refractory pancytopenia after obtaining informed consent. She showed an improvement in pancytopenia and became transfusion independent. After 1 year of eltrombopag treatment, bone marrow examination revealed 0.7% blasts with the karyotype 46,XX[20] and without monosomy 7 clone by FISH analysis. After a further 1 year of eltrombopag treatment with dose tapering, she has achieved a complete response. This case suggested that eltrombopag treatment is not necessarily contraindicated in patients with monosomy 7.

Although several pedigrees of familial myelodysplastic syndromes/acute myeloid leukemia (fMDS/AML) have been reported, the epidemiology and clinical features has been poorly understood. To explore the epidemiology of this entity, we performed a retrospective nationwide epidemiological survey in Japan using questionnaire sheets. The questionnaire was sent to 561 institutions or hospitals certified by Japanese Society of Hematology, unearthing the existence of 41 pedigrees of fMDS/AML. Among them, we obtained the clinical information of 31 patients in 20 pedigrees. The median age of the initial diagnosis was 51 years (range 9-88 years) and the WHO classification 2008 ranged from refractory anemia (RA) to AML. Focusing on the familial MDS patients, refractory anemia with excess blasts (RAEB)-2 was the largest group (27.3%). The median overall survival (OS) of fMDS and fAML in this study were 71.6 and 12.4 months, and the five-year OS were 61.3 and 50%, respectively.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment for chronic myelomonocytic leukemia (CMML); however, factors predicting allo-HSCT outcomes for CMML have not been well defined. This study assessed whether the existing five scoring systems for CMML prognosis could be applied for predicting allo-HSCT outcomes. We retrospectively evaluated 38 patients who underwent allo-HSCT for CMML from 2000 to 2014. At 3 years, overall survival (OS) and disease-free survival were 34.6 and 24.7%, respectively. According to the risk stratification at the time of transplantation, only the CMML-specific cytogenetic risk scoring system could successfully predict transplantation outcomes. At 3 years, OS was 56.7, 12.5, and 0% (p = .01) in the low, intermediate, and high-risk groups. Our data suggest that the CMML-specific cytogenetic risk stratification at transplant may be useful for identifying patients with CMML who may benefit from HSCT. However, further studies are warranted to confirm this observation.

Objectives: The D-index and the L-index, calculated as the area over the neutrophil and lymphocyte curves, respectively, reflect both the intensity and duration of cytopenia. We, retrospectively, investigated the impact of these indexes on pulmonary infection (PI) in induction chemotherapy for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL)., Methods: We included 92 patients (ALL 83, LBL 9) from two institutions. We calculated the D-index and cumulative D-index until the development of PI (c-D-index), which enables real-time risk assessment for infection. We also calculated the L-index (35), defined as the area over the lymphocyte curve during lymphopenia (<700/µl) until day 35 and the cumulative-L-index until the development of PI (c-L-index)., Results: Eight patients developed PI on day 20 (median). Two patients were strongly suspected to have bacterial pneumonia, and the others were suspected to have pulmonary fungal infection. The D-index and the L-index (35) in patients with PI were higher than those in patients without PI (7230 ± 4734 vs. 4519 ± 3416, P = 0.041 and 15 458 ± 5243 vs. 8920 ± 5901, P = 0.018), while the c-D-index and the c-L-index were not significantly different. Although the c-L-index did not have predictive value for PI, c-D-index, when treated as a dichotomous variable with a cutoff value of 5589 as determined by a receiver operating characteristic curve analysis, showed a significant difference between two groups (P = 0.045). This association became clearer when we focused on suspected pulmonary fungal infection., Discussion and Conclusion: In induction chemotherapy for ALL/LBL, c-D-index with a cutoff value of 5589 might have predictive value for the development of PI.

Elderly patients with non-Hodgkin lymphoma (NHL) have a poor prognosis. Owing to treatment-related toxicities, there is no standard chemotherapy for the elderly patients, especially those aged 70 years or older. In this study, we retrospectively evaluated the efficacy and toxicity of reduced-dose (two-thirds) R-CHOP chemotherapy as an initial chemotherapy for 45 patients aged 70 years or older with B-cell NHL. The WHO classification of NHL included diffuse large B-cell lymphoma (DLBCL) (31), mantle cell lymphoma (5), follicular lymphoma (4), extranodal marginal zone lymphoma (1), Burkitt lymphoma (1), and B-cell lymphoma whose further types were unclassified (3). The incidences of grade 4 neutropenia and febrile neutropenia (FN) were 51.1 and 15.6%, respectively. Efficacy was evaluated in patients with DLBCL. The overall and complete response (CR) rates were 96.7 and 90.0%, respectively. Two-year event-free survival (EFS) and overall survival (OS) were 84.4 and 89.2%, respectively. There was no treatment-related mortality. In conclusion, two-thirds R-CHOP chemotherapy is a promising treatment for elderly patients with B-cell NHL in terms of its efficacy and toxicity.

A study to evaluate WT1 mRNA expression levels in peripheral blood (PB) and bone marrow aspirate (BM) was conducted in 172 patients, including 115 with myelodysplastic syndromes (MDS), in Japan. The level of WT1 mRNA expression was evaluated according to the French-American-British (FAB) and World Health Organization (WHO) classifications (2001, 2008) and using the International Prognostic Scoring System and the WHO Prognostic Scoring System scales. WT1 mRNA expression levels in PB and BM were well correlated (r = 0.85), and they tended to increase with disease stage progression and in those at higher risk of leukemic transformation. WT1 mRNA expression can be a useful marker for the diagnosis and risk evaluation of MDS.

The incidence of autoimmune hemolytic anemia (AIHA) is highest among the elderly, and thus it is frequently associated with co-morbidities such as diabetes mellitus (DM). However, there have been few reports on the impact of these co-morbidities on survival in patients with AIHA. Therefore, we retrospectively reviewed the records of 53 consecutive AIHA patients and assessed the impact of DM on survival. Eighteen of the 53 patients had DM. The estimated 4-year overall survival (4y-OS) for all patients was 84.9%. Infection was the most frequent cause of death, and fatal infections were exclusively observed in patients with DM. The deaths in DM patients occurred frequently within 1 year, to give significantly poor survival (4y-OS; 69.3% versus 93.6%, P=0.0064). The presence of DM was identified as the only significant risk factor for survival. A large prospective investigation is warranted to assess the impact of co-morbidities on survival in patients with AIHA.

Fas-ligand (FasL) is a member of the tumor necrosis factor family and transmits apoptotic cell death signal by binding to its receptor, Fas. FasL is expressed on the cell surface of activated T-cell and natural killer (NK) cell. It has been shown that the FasL can be released from the cell surface by metalloproteinase. The serum soluble FasL (sFasL) is increased in some patients with NK cell lymphoma/large granular lymphocytic leukemia. We have recently seen a patient with recurrent B-cell lymphoma accompanied with an increased serum sFasL level after autologous peripheral blood stem cell transplantation. The sFasL was markedly decreased with the tumor regression induced by the chemotherapy. We present here the first case of an elevated serum sFasL level associated with B-cell lineage malignancy and discuss the possible clinical value of sFasL.