Myelofibrosis (MF) is a myeloproliferative neoplasm associated with significant morbidity and mortality, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative ...approach. While the optimal conditioning regimen before allo-HSCT for MF patients remains to be determined, recent studies have suggested that a thiotepa-busulfan-containing dual-alkylator regimen, FBT regimen, may be associated with favorable outcomes. In Japan, however, thiotepa is not indicated for MF. Here we describe the results of 6 cases of MF treated with melphalan-busulfan containing dual-alkylator regimen, FBM regimen, followed by their first allo-HSCT at a single institution. Neutrophil and platelet engraftment was achieved in all patients. And a full donor chimerism was confirmed in all patients at ＋30 days after allo-HSCT. The relatively small size and short observation period of our study make it difficult to draw a definitive conclusion ; however, our results suggest that a dualalkylator regimen of FBM may be a candidate for an conditioning for allo-HSCT for MF, which should be verified with a large cohort of patients.
Introduction : Treatment outcome of adult patients with acute B-cell lymphoblastic leukemia (ALL) is suboptimal even after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). To ...maximize the efficacies of this treatment strategy, risk stratification is crucial. Methods : We retrospectively collected clinical data of the adult patients with allo-HSCT for ALL at a single insitiution in Japan between 2003 and 2022. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS), progression-free survival (PFS) and GVHD-free-and-relapse-free survival (GRFS) at 3 years. Results : A total of 58 patients were included with 34 females and a median age of 39. Sixty-two percent of patients harbored high-risk cytogenetic features or Philadelphia chromosome (Ph). Hematologic complete response (CR) rate was 93％ after a first induction, but 75.9％ were in CR at allo-HSCT. Blinatumomab was used in 1.7％ of patients. A chimeric mRNA had been detected in 4 of 26 patients at allo-HSCT. The 3-year OS, PFS and GRFS were 72.7％, 54.7％ and 46.2％, respectively. Pre-transplantation CR was an independent risk factor. Discussion/Conclusions : Our results imply that a better OS may potentially be achieved by improved pretransplantation CR rate with more frequent application of novel agents.
Leukemia may rarely develop in a woman during pregnancy, posing clinical challenges to the patient, fetus, family, and medical staff managing malignancy and pregnancy. We retrospectively analyzed ...cases of pregnancy‐associated leukemia consecutively diagnosed and treated at a local tertiary‐care hospital in Nagano, Japan, over the past 20 years. Five cases were identified among 377,000 pregnancies in the area (one in every 75,000 pregnancies), all involving acute leukemia (three acute myelogenous leukemia AML and two acute lymphoblastic leukemia ALL). The cases were diagnosed in the first trimester (n = 1), second trimester (n = 3), or third trimester (n = 1). There were no apparent pregnancy‐associated delays in diagnosing and treating the cases. Three patients underwent induction chemotherapy during pregnancy, two of whom eventually delivered healthy babies. One of the five patients chose abortion before chemotherapy initiation. Two cases showing high‐risk features at the diagnosis (AML with an FLT3‐ITD mutation n = 1 and relapsed ALL n = 1) eventually died despite consolidative allogeneic hematopoietic stem cell transplantation. Our results suggested that patients with pregnancy‐associated acute leukemia can be treated similarly to nonpregnant patients, although pregnancy imposes particular clinical challenges that should be resolved with multidisciplinary care.
Tumor lysis syndrome (TLS) is a rare complication of the treatment for chronic lymphocytic leukemia (CLL). Since the advent of new therapeutic agents with higher response rates, however, TLS has been ...observed with increasing frequency. An 84-year-old woman with a nine-year history of untreated CLL presented with exacerbating dyspnea due to pleural effusion. CLL cells without Richter transformation were observed in the pleural effusion at a high concentration, as well as in lymph nodes and bone marrow. After 5 days of oral fludarabine and cyclophosphamide (FC) therapy, the patient developed TLS, which necessitated rescue with hemodialysis. Although transient exacerbation of pleurisy occurred, the effusion cytology ameliorated, and she eventually achieved complete remission after additional two courses of FC and rituximab. Sequestration of fludarabine in the pleural effusion may be attributable to the development of TLS.
We report here a case of a 37-year-old man with human immunodeficiency virus (HIV) infection followed by JC virus (JCV) infection and primary central nervous system lymphoma (PCNSL). The patient had ...been infected with HIV type 1 due to blood products for hemophilia A during infancy. He had progression of nervous symptoms and was diagnosed with progressive multifocal leukoencephalopathy (PML) clinically at the age of 36, when his CD4-positive lymphocyte counts ranged between 350 and 450/μl. Oral mefloquine, intravenous methylprednisolone pulse therapy, and intravenous immunoglobulin were not effective for the PML, and the patient entered a vegetative state. Brain biopsy revealed JCV infection without pathological findings of PML. Eight months after the clinical diagnosis of PML, he developed respiratory failure and brain magnetic resonance imaging revealed a mass lesion in the brain stem. The patient died 19 months after the diagnosis of PML. Autopsy findings were compatible with PCNSL. EBV-encoded small RNA-1-positive cells were not detected. We present a case of JCV-positive PCNSL with HIV infection complicated with clinical PML.
We report here a case of a 70-year-old male with myelodysplastic/myeloproliferative neoplasms (MDS/MPN) having hepatosplenomegaly, mild monocytosis, and normal karyotypes without JAK2 mutation. The ...patient developed an acute transformation and during the intensive therapy with daunorubicin and cytarabin, diffuse alveolar hemorrhage appeared due to disseminated intravascular coagulopathy. After induction, bone marrow blasts reduced to 5.1%, and the patient received two courses of azacitidine therapy. During these courses, blasts in the peripheral blood were not observed. Intensive chemotherapy consisting of daunorubicin and cytarabin followed by azacitidine therapy might be effective for acute transformation in MDS/MPN.
We report here a case of a 37-year-old man with human immunodeficiency virus (HIV) infection followed by JC virus (JCV) infection and primary central nervous system lymphoma (PCNSL). The patient had ...been infected with HIV type 1 due to blood products for hemophilia A during infancy. He had progression of nervous symptoms and was diagnosed with progressive multifocal leukoencephalopathy (PML) clinically at the age of 36, when his CD4-positive lymphocyte counts ranged between 350 and 450/μl. Oral mefloquine, intravenous methylprednisolone pulse therapy, and intravenous immunoglobulin were not effective for the PML, and the patient entered a vegetative state. Brain biopsy revealed JCV infection without pathological findings of PML. Eight months after the clinical diagnosis of PML, he developed respiratory failure and brain magnetic resonance imaging revealed a mass lesion in the brain stem. The patient died 19 months after the diagnosis of PML. Autopsy findings were compatible with PCNSL. EBV-encoded small RNA-1-positive cells were not detected. We present a case of JCV-positive PCNSL with HIV infection complicated with clinical PML.
Introduction: Treatment outcome of adult patients with acute B-cell lymphoblastic leukemia (ALL) is suboptimal even after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). To ...maximize the efficacies of this treatment strategy, risk stratification is crucial. Methods: We retrospectively collected clinical data of the adult patients with allo-HSCT for ALL at a single insitiution in Japan between 2003 and 2022. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS), progression-free survival (PFS) and GVHD-free-and-relapse-free survival (GRFS) at 3 years. Results: A total of 58 patients were included with 34 females and a median age of 39. Sixty-two percent of patients harbored high-risk cytogenetic features or Philadelphia chromosome (Ph). Hematologic complete response (CR) rate was 93% after a first induction, but 75.9% were in CR at allo-HSCT. Blinatumomab was used in 1.7% of patients. A chimeric mRNA had been detected in 4 of 26 patients at allo-HSCT. The 3-year OS, PFS and GRFS were 72.7%, 54.7% and 46.2%, respectively. Pre-transplantation CR was an independent risk factor. Discussion/Conclusions: Our results imply that a better OS may potentially be achieved by improved pretransplantation CR rate with more frequent application of novel agents.
Large granular lymphocytic leukemia (LGLL) is a heterogenous group of disorders. The clinical presentations of LGLL are highly variable; it may present with neutropenia or anemia, complicated with ...recurrent infections, autoimmune diseases such as rheumatoid arthritis, and neurological symptoms, requiring therapeutic interventions. It may present only with indolent laboratory changes without any symptoms. The cytological phenotypes of LGLL also vary and they commonly include CD8+TCR αβ-type, CD4+TCR αβ-type, and NK cell-type. NK cell-type LGLL is designated as chronic lymphoproliferative disorder of NK cells (CLPD-NK). TCR γδ-type LGLL (γδT-LGLL) is even rarer and it often confers cytopenia.
The genetic backgrounds of LGLL with CD8+TCRαβ-type, CD4+TCRαβ-type and NK cell-type have been elucidated with the recent sequencing technologies. JAK/STAT signaling genes and chromatin-modifying genes were frequently mutated in the non-leukemic counterpart of the lymphoid malignancies with γδ TCR immunophenotypes, such as hepatosplenic T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma and primary cutaneous gamma delta T-cell lymphoma. However, the genetic basis of γδT-LGLL and the genetic-phenotypic associations remain unclear.
The aim of this study is to identify clinical and genetic characteristics of γδT-LGLL in comparison with other LGL leukemias.
In total, 56 LGLL patients were recruited; six patients with γδT-LGLL, 25 CD8+ TCRαβ type, 8 CD4+TCR αβ type and 17 CLPD-NK, in this study. All cases were negative for EBV. The median age of patients with γδT-LGLL was 48 years old and five of them were male. The median LGL counts and hemoglobin level were 1.81 ×109/L (range; 0.60-4.42) and 5.8 g/dL (range; 3.0-11.2), respectively. All patients with γδT-LGLL had anemia and/or neutropenia, although no patients were thrombocytopenic. 4 patients presented with pure red cell aplasia. Common immunophenotypes of γδT cells were CD2+ CD3+ CD4-CD7+. 3 patients were CD8+. CD16, CD56 and CD57 were positive in 3, 0, and 1 patient, respectively. γδT cells of all patients showed a monoclonal pattern of TCRγ gene rearrangements with BioMed 2 protocol. We performed amplicon sequencing of entire coding regions of STAT3, STAT5B and TNFAIP3 genes and allele-specific PCR for several hot spot regions of STAT3 and STAT5B genes using extracted DNA from mononuclear cells of peripheral blood. Mutations in STAT3 and TNFAIP3 were identified in 100% (6/6) and 17% (1/6), respectively. Among the10 STAT3 mutations identified, 5 were located in the SH-2 domain, while other 3 were in coiled-coiled domain and the other 2 were in the DNA binding domain. The median variant allele frequencies of STAT3 was 2.0% (0.7-22.6) and STAT3 mutations were restricted to sorted γδT cells in all 3 patients examined. No patient was positive for STAT5B mutations, including N642H and Y665F with allele specific PCRs. One of 5 patients who were treated with cyclosporin A was refractory. Two patients were treated with cyclophosphamide, showing clinical improvements. The patients with γδT-LGLL were younger than those with other types of LGLL (P=0.048) and anemia and STAT3 mutations were significantly more frequent in γδT-LGLL (P value; 0.003 and 0.02, respectively). PRCA was a consistent cause of anemia in γδT-LGLL. Low frequency of STAT5B mutations among γδT-LGLL patients was in contrast to other aggressive γδT cell lymphoma in which STAT5B frequently mutated. The clinical characteristics of γδT-LGLL patients may be defined by younger age and the anemia due to pure red cell aplasia, and the frequent STAT3 mutations might be a novel molecular marker for γδT-LGLL.
Yamane:Pfizer: Research Funding; Celgene: Honoraria; Bristol-Meyers Squibb: Research Funding; Chugai Pharmaceutical: Consultancy, Research Funding; Astellas Pharma: Research Funding; Eli Lily and Company: Research Funding. Ishida:Eli Lily and Company: Research Funding; Astellas Pharma: Research Funding; Pfizer: Research Funding; Bristol-Meyers Squibb: Research Funding; Chugai Pharmaceutical: Consultancy, Research Funding; Celgene: Honoraria.
•A nationwide epidemiologic study for acquired PRCA identified 1055 patients, an incidence rate of 1.06 patients per million per year.•The median age was 73 years old with female predominance ...(1.5:1), and 69% of the PRCA was idiopathic.
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Acquired pure red cell aplasia (PRCA) is a rare syndrome characterized by anemia with reticulocytopenia and a marked reduction in erythroid precursors. Given its rarity, the true incidence is largely unknown, and epidemiological data representing the general population, with a description of the full spectrum of etiologies, are scarce. An epidemiological study on PRCA in Japan conducted 30 years ago estimated the annual incidence as 0.3 per million. To update the data and investigate the incidence and demographics of PRCA, we conducted a nationwide epidemiological study using the Japanese Society of Hematology (JSH) Hematologic Disease Registry, a hematologic disease registration database managed by the JSH and the Diagnosis Procedure Combination (DPC) study data available at a website of the Ministry of Health, Labor, and Welfare (MHLW) of Japan. A total of 1055 patients with newly diagnosed acquired PRCA were identified between 2012 and 2019, and the average annual incidence was calculated at 1.06 (95% confidence interval CI, 0.83-1.28) per million. The median age was 73 (range, 18-99) years. The female-to-male ratio was 1.5:1, and the female predominance was most prominent in the child-bearing age group. Sixty-nine percent of acquired PRCA was idiopathic. The incidence of PRCA was approximately 20% of that of aplastic anemia (AA) during the same period. Approximately 0.98 patients per million per year (95% CI, 0.89-1.07) required hospitalization for the treatment of PRCA. These results are expected to contribute to the discussion of resource allocation for PRCA in the aging population in many countries, including Japan.
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