We performed a retrospective population-based cohort study of acute myeloid leukemia (AML) in Miyazaki Prefecture, Japan. Over 6 years, we diagnosed 221 patients (211 adults and 10 children) with ...AML, indicating an incidence of AML in Miyazaki Prefecture of 3.2 per 100,000 per year. In 193 adult patients with non-acute promyelocytic leukemia (APL), the proportion of patients with myelodysplasia, unfavorable risk karyotypes, antecedent hematologic diseases, prior chemotherapy for other malignancies, and small proportion of blasts in the marrow was higher in patients ≥65 years, and patients with poor performance status (PS) and higher WBC counts at diagnosis were more prevalent among patients ≥75 years. One-third of the adult non-APL patients met the inclusion criteria usually applied in clinical trials: de novo AML, age ≤64 years with PS 0–2 and no key organ dysfunction. The 5-year overall survival (OS) rate of adult non-APL patients was 21.1 % (patients ≤64 years, 33.8 %; 65–74 years, 21.6 %; ≥75 years, 0 %). Multivariate analysis revealed that French-American-British subtypes M0, M6, and M7, poor PS (3, 4), unfavorable risk karyotypes, and higher WBC counts at diagnosis were independent adverse prognostic factors associated with OS. This analysis provides real world data.
We report a 29-year-old Japanese male with acute myelogenous leukemia (AML)-M4 with a cryptic t(7;11)(p15;p15), in which a chimeric
NUP98-HOXA9
fusion was detected by polymerase chain reaction ...analysis and a chromosomal analysis showed 46,XY. The patient received intensive chemotherapy and underwent autologous stem cell transplantation, and remission was confirmed by the disappearance of
NUP98-HOXA9
. However, 6 months after transplantation, the patient relapsed;
NUP98-HOXA9
was detected again and karyotypic analysis revealed 46,XY, t(1;21)(p32;q22). Fluorescent in situ hybridization (FISH) analysis using an
AML1-ETO
translocation dual probe, showed that the 21q22 breakpoint involved
AML1
locus. A retrospective FISH analysis showed that t(1;21) was absent at onset. This is the first reported case with AML who had a cryptic t(7;11)(p15;p15), and additionally acquired t(1;21)(p32;q22) at relapse.
In the present study, we aimed to clarify the capacity of human cord blood‐ and bone marrow‐ derived progenitor cells to generate gastrointestinal epithelial cells in clinical and experimental ...transplantation settings. First, in a clinical transplantation setting, gastrointestinal tissues derived from female pediatric or juvenile recipients of allogeneic sex‐mismatched bone marrow and cord blood transplantation were examined for the presence of donor‐derived epithelial cells. Gastrointestinal specimens of allogeneic recipients included Y chromosome+ cytokeratin+ epithelial cells at a frequency of 0.4–1.9%. To further determine the capacity of purified human progenitor cells, human cord blood‐ or bone marrow‐derived CD34+ cells were transplanted into newborn NOD/SCID/β2‐microglobulinnull mice as an experimental transplantation assay. When gastrointestinal tissues derived from recipient mice were subjected to FISH and immunofluorescence analyses, human epithelial cells were identified at a frequency of 0.24– 0.58% at 3 months posttransplantation. Finally, double FISH analyses using species‐specific probes revealed that human chromosome+ epithelial cells did not possess any murine chromosomes, indicating that donor‐derived epithelial cells were not generated only by cell fusion. On the basis of these findings, it is concluded that purified human cord blood and bone marrow CD34+ progenitor cells can generate gastrointestinal epithelial cells across allogeneic and xenogeneic histocompatibility barriers.
Background: Cord blood is an alternative donor source for patients without HLA-matched donors. Calcineurin inhibitors (CNIs) alone, as prophylaxis for graft-versus-host disease (GVHD) in cord blood ...transplantation (CBT) patients, reportedly increase the incidence of severe pre-engraftment immune reaction (PIR), leading to transplant-related mortality (TRM) with primary engraft failure and multiple organ dysfunctions. Therefore, additional immunosuppressive agents are needed. Reportedly, short-term methotrexate (sMTX) plus CNIs improved outcomes in patients receiving CBT with full-intensity conditioning (FIC) regimens; however, safety and efficacy of sMTX plus cyclosporine have not been assessed in patients receiving CBT with reduced-intensity conditioning (RIC) regimens. Methods: We retrospectively analyzed 43 patients who received single-unit CBT and were treated with sMTX plus cyclosporine (RIC group, 15; FIC group, 28). Results: Neutrophil engraftment rate was significantly lower in RIC group (53.3%) than in FIC group (78.6%, P=0.04). Cumulative incidence of TRM tended to be higher in the RIC group than in the FIC group (P=0.12); the leading cause of death in the RIC group was bacterial infections. Conclusions: sMTX plus cyclosporine does not seem feasible for treating patients receiving single-unit CBT following RIC. MTX dose optimization or alternative immunosuppressive agent application should be considered in such patients.
Malignancy is a fatal complication of end-stage renal disease (ESRD) requiring haemodialysis. However, the successful treatment of haematological malignancies has been rarely reported. We describe ...the case of a 63-year-old man who presented with IgA-type multiple myeloma (MM; Durie–Salmon stage IIIB) derived from monoclonal gammopathy of undetermined significance concomitant with ESRD due to diabetic nephropathy. First, haemodialysis was initiated before chemotherapy, and bortezomib and dexamethasone were found to be ineffective. Subsequently, 8 courses of dose-adjusted lenalidomide therapy were administered according to the degree of haematological and renal functions. The patient remained in partial remission without disease progression for 21 months. Thus, lenalidomide therapy is effective for bortezomib-refractory MM concomitant with ESRD.
We retrospectively analyzed 38 patients with AML who received azacitidine (AZA) to treat disease relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with objective ...response (OR) (n = 20) after AZA had significantly higher 2-year overall survival (OS) (45.0% vs 5.6%; p = 0.004) than progressive disease. The 2-year OS was significantly higher in the retransplant group (n = 23) than in the nonretransplant group (n = 15) (34.8% vs 13.3%; p = 0.034). We analyzed 167 patients who underwent the second allo-HSCT to clarify the impact of pretransplant AZA after the second allo-HSCT. Patients in the AZA group (n = 21) had significantly higher 2-year disease-free survival (DFS) (32.7% vs 14.5%; p = 0.012) and OS (38.1% vs 17.5%; p = 0.044) than those in the SOC group (n = 146). Our data demonstrate that AZA is an effective and well-tolerated bridging therapy to the second allo-HSCT.
Portal vein thrombosis is a rare, aggressive and life-threatening complication of liver cirrhosis (LC). Eltrombopag is effective for the treatment of chronic hepatitis with thrombocytopenia, and ...portal vein thrombosis at this time has rarely been reported. We describe the case of a 78-year-old woman who suffered from LC due to hepatitis C viral infection. The patient developed immune thrombocytopenic purpura (ITP) that was diagnosed on the basis of nasal bleeding, progressive severe thrombocytopenia, elevation of platelet-associated IgG (PAIgG), no response to the transfusion of platelets and no abnormal findings on bone marrow biopsy. Although we first administered prednisolone (0.5mg/kg/day), there was no recovery of platelet function and the nasal bleeding persisted. Subsequently, we administered eltrombopag for refractory ITP at a dose of 12.5mg/day, and the thrombocytopenia gradually improved. Fifty-four days after the start of eltrombopag therapy, she developed portal vein thrombosis. Eltrombopag was stopped immediately, and antithrombin III was administered for prophylaxis against further portal vein thrombosis. Despite these treatments, there were subsequent deep vein and pulmonary artery thromboses. We then administered heparin for recanalization of the thrombi. One month after the initiation of heparin, there was recanalization as well as improvements of the portal vein, deep vein and pulmonary artery thromboses. There was no further thrombosis progression after switching from heparin to warfarin therapy. Our case suggests that eltrombopag may increase the risk of portal vein thrombosis ; therefore, this drug must be used carefully in the treatment of ITP in patients with LC due to hepatitis C viral infection. J Clin Exp Hematop 53(2):151-155, 2013
Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a rare disease, which presents with features of myelodysplastic syndromes with ring ...sideroblasts and essential thrombocythemia, as well as anemia and marked thrombocytosis.
SF3B1
and
JAK2
mutations are often found in patients, and are associated with their specific clinical features. This study was a retrospective analysis of 34 Japanese patients with MDS/MPN-RS-T. Median age at diagnosis was 77 (range, 51–88) years, and patients had anemia (median hemoglobin: 9.0 g/dL) and thrombocytosis (median platelet count: 642 × 109/L). Median overall survival was 70 (95% confidence interval: 68-not applicable) months during the median follow-up period of 26 (range: 0–91) months. A
JAK2
V617F mutation was detected in 46.2% (n = 12) of analyzed patients (n = 26), while an
SF3B1
mutation was detected in 87.5% (n = 7) of analyzed patients (n = 8). Like those with myelodysplastic syndromes or myeloproliferative neoplasms, patients often received erythropoiesis-stimulating agents and aspirin to improve anemia and prevent thrombosis. This study, which was the largest to describe the real-world characteristics of Japanese patients with MDS/MPN-RS-T, showed that the patients had similar characteristics to those in western countries.
Secondary malignancies that develop after allogeneic-hematopoietic stem cell transplantation (allo-HSCT) have become serious issues. A 47-year-old man who developed acute myeloid leukemia in 2009 and ...subsequently underwent allo-HSCT twice: in 2009 and 2011. In 2015, voriconazole for lung aspergillus was started. In 2018, chronic graft-versus-host disease (GVHD) and multiple actinic keratoses manifested at his head. In 2020, some lesions were diagnosed as squamous cell carcinoma, so voriconazole was withdrawn, and subsequent surgery and radiation led to remission. Long-term administration of voriconazole in addition to allo-HSCT and chronic GVHD may be closely related to secondary skin cancer.
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