[Multiple extramedullary plasmacytomas responding to a reduced dose of carfilzomib following drug-induced thrombotic microangiopathy].

Herein, we report the findings of a 79-year-old male patient who presented with multiple extramedullary plasmacytomas following a relapse of primary plasma cell leukemia. He developed thrombotic microangiopathy (TMA) while receiving carfilzomib, lenalidomide, and dexamethasone (KLd) therapy. He was diagnosed with plasma cell leukemia 3 years ago; he demonstrated a very good partial response (VGPR) after undergoing two regimens, including either bortezomib or lenalidomide, and he had been followed up without any other treatment due to complications of infection. Following relapse, KLd was initiated. On day 7 of KLd, TMA developed; therefore, the treatment was discontinued. The TMA improved only with the discontinuation of KLd. A reduced dose of KLd was readministered; the TMA did not relapse. He demonstrated VGPR after three courses of reduced-KLd; he has since remained in remission through ten courses. Therefore, carfilzomib therapy may be useful in relapsing and refractory cases. Drug-induced TMA has been reported to be caused by either immune-mediated or dose-dependent toxicity mechanisms. In patients who develop dose-dependent TMA with carfilzomib, dose reduction could be considered in cases showing an effective response to the treatment.

Does time of CCI measurement affect the evaluation of platelet transfusion effectiveness?

The measurement of corrected count increment at 1-h post-transfusion (CCI-1 h) of platelet concentrate (PC) transfusion is recommended, but in the revised Japanese Guideline (2017) it was changed to "after 10-min to 1-h", following the revision of the guidelines from Western countries. Here, we aimed to investigate on the feasibility to apply the CCI measured at 10-min or 30-min post-transfusion as the surrogate of CCI-1 h. Peripheral blood was collected at 10-min, 30-min and 1-h post-transfusion of PC and the effectiveness of the transfusion was analyzed based on the CCI. In the period from December 2017 to February 2020, 8 patients, who received multiple PC transfusion (total 208) at our institution, were analyzed. We performed the univariate analyses to examine the relationship between CCI value and the categorical variables, p-value <0.1 was obtained for gender (p = 2.91 × 10-19), fever after transfusion (p = 0.0163). The qualitative variables, namely measurement time (p = 0.0553), also showed p-value <0.1. Using these factors as covariates in the mixed effect model, we found that the measurement time (p = 0.0007) had a significant effect on the CCI value when looking at fixed effects. Although there is a tendency for decreased CCI values with time progression, the slope of the change in the mixed model was -0.00307, indicating that the CCI difference among the 3 measurements was small. Here we provide evidence that CCI measured at 10-min and 30-min post-transfusion give results comparable to those measured at 1-h post-transfusion, under the Japanese practice of platelet transfusion, which relies on 100 % single-donor apheresis PC, and ABO-identical whenever possible.

Azacitidine-associated haemorrhagic enteritis in a case of myelodysplastic syndrome: A case report.

WHAT IS KNOWN AND OBJECTIVE: 5-Azacitidine (AZA) is an agent widely used to treat myelodysplastic syndrome (MDS). CASE DESCRIPTION: We herein report an 83-year-old woman diagnosed with MDS who was treated with AZA. She tolerated the first cycle of AZA; however, severe adverse events involving haemorrhagic enteritis with multiple intestinal ulcers developed after the second and third cycles. Additionally, the interval between the administration of AZA and the development of haematochezia shortened with each cycle of AZA. WHAT IS NEW AND CONCLUSION: We herein report as-yet-undescribed potential side effects, AZA-associated haemorrhagic enteritis that should be kept in mind.

Multiple HLA-matched platelet transfusions for a single patient with broad anti-HLA antibodies: a case report.

The efficacy of 30 platelet concentrate (PC) products transfused to a patient with myelodysplastic syndrome (MDS) was evaluated by calculating the 1-hour post-transfusion corrected count increment (1h-CCI). Of the 30 transfusions, all HLA-A/B-matched, the cross-match (CM) test was negative in 23 (CM(-)-PC) and weakly positive (CM(+)-PC) in 2, and the CM test was not conducted in 5 (non-CM-PC). The effective rate was higher with CM(-)-PC compared to non-CM-PC (82.6% vs 60%), but statistical significance was not achieved, which suggested that the CM test of PC may still be a not satisfactorily effective predictor of PC refractoriness. Studies are ongoing in Japan to confirm on the importance of CM test of PC.

Phase II study of imatinib-based chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia.

This study investigated the efficacy of imatinib based therapy with intensified consolidation therapy in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) to prevent early relapse. We conducted a phase II trial of imatinib-combined chemotherapy for newly diagnosed BCR-ABL-positive ALL in adults. Sixty-eight patients were included in the trial between October 2008 and December 2010. The median age was 49 years, with 28 patients >55 years of age. Sixty-five patients achieved CR (95.6%). The estimated 2-year event-free survival (EFS) and overall survival (OS) were 62.3% and 67.4%, respectively. Allogeneic stem cell transplantation (allo-SCT) at initial CR was performed in 43 patients. Thirty-five of 39 patients <55 years and 8 of 26 patients >55 years underwent allo-SCT at first CR. The 3-year OS in patients <55 years receiving allo-SCT at first CR, patients >55 years receiving allo-SCT at first CR, patients <55 years not receiving allo-SCT at first CR, and patients >55 years not receiving allo-SCT at first CR were 80.4%, 41.1%, 32.5%, and 52.0%, respectively (P = 0.058). The three-year EFS in each group was 76.7%, 53.6%, not reached, and 26.4%, respectively (P = 0.150). A high CR rate was observed with imatinib-based chemotherapy allowing allo-SCT in a high proportion of patients, particularly those <55 years. Moreover, intensified consolidation therapy reduced early relapse rates following induction therapy and resulted in improved OS and EFS rates following allo-SCT. This trial was registered with the UMIN (000001226).

Early-onset herpes simplex encephalitis type 1 triggered by COVID-19 disease: A case report.

Coronavirus disease 2019 (COVID-19) causes a systemic inflammatory response and a temporary immunosuppression of hosts. Several reports have showed that reactivation of herpes simplex virus type 1 (HSV-1) is strongly associated with COVID-19. We present a case of a 66-year-old female, who developed HSV-1 encephalitis, showing impaired consciousness and typical MRI findings such as hyperintense lesions in the temporal lobe, insular cortices, bilateral medial frontal lobe on diffusion-weighted imaging, 7 days after the onset of COVID-19 symptoms. The number of cases of encephalitis in patients with COVID-19 is increasing. However, there has been limited reports of HSV-1 encephalitis following COVID-19, especially for cases with an interval of 7 days or less from the onset of COVID-19 symptoms to the onset of HSV-1 encephalitis. Our case highlights the importance of considering HSV-1 encephalitis in the differential when managing a patient with COVID-19-associated neurologic complications, even if it is in the early stages of COVID-19.

Recipient PTPN22 -1123 C/C genotype predicts acute graft-versus-host disease after HLA fully matched unrelated bone marrow transplantation for hematologic malignancies.

PTPN22 is a critical negative regulator of T cell responses. Its promoter gene variant (rs2488457, -1123G>C) has been reported to be associated with autoimmune diseases. This study analyzed the impact of the PTPN22 variant on transplantation outcomes in a cohort of 663 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. The recipient C/C genotype versus the recipient G/G genotype resulted in a lower incidence of grade II-IV acute graft-versus-host disease (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.29-0.85; P = .01), as well as a higher incidence of relapse (HR, 1.78; 95% CI, 1.10-2.90; P = .02), as demonstrated on multivariate analysis. In patients with high-risk disease, the recipient C/C genotype was associated with significantly worse overall survival rates than the recipient G/G genotype (HR, 1.60; 95% CI, 1.02-2.51; P = .04), whereas this effect was absent in patients with standard-risk disease. In addition, the donor G/C genotype was associated with a lower incidence of relapse (HR, 0.58; 95% CI, 0.40-0.85), which did not influence survival. Our findings suggest that PTPN22 genotyping could be useful in predicting prognoses and creating therapeutic strategies for improving the final outcomes of allogeneic BMT.

The recipient CXCL10 + 1642C>G variation predicts survival outcomes after HLA fully matched unrelated bone marrow transplantation.

CXCL10 is a chemoattractant for immune cells that is involved in several immune-inflammatory disorders. This study retrospectively examined the impact of a single nucleotide variation (rs3921, +1642C>G) in the CXCL10 gene on transplant outcomes in a cohort of 652 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies. The recipient C/G or G/G genotype was found to be associated with a significantly better 5-year overall survival (OS) rate and a lower transplant-related mortality (TRM) rate than the recipient C/C genotype. The recipient C/G or G/G genotype also predicted a reduced incidence of death due to organ failure. The multivariate analysis showed the recipient C/G or G/G genotype to exhibit statistical trends toward beneficial effects on OS but not on TRM. CXCL10 genotyping could therefore be useful in predicting prognoses and creating therapeutic strategies for improving the final outcomes of patients who undergo allogeneic BMT.

Myeloid leukemoid reaction after initial azacitidine therapy for chronic myelomonocytic leukemia.

The development of myeloid leukocytosis in leukemia patients during antileukemic treatment requires a differential diagnosis between myeloid leukemoid reaction and leukemia progression. We herein report the case of an 80-year-old Japanese man with chronic myelomonocytic leukemia (CMML) who developed marked myeloid leukocytosis (36.3 × 109/L) with 32.5% monocytes and 48% neutrophils about 4 weeks after the initial 5-azacitidine (AZA) treatment. The leukocytosis was unlikely to be attributed to infection and adverse drug reaction. As it resolved in a few days without any interventions, the transient myeloid leukocytosis was confirmed to be a myeloid leukemoid reaction. After four cycles of AZA treatment, leukemic blasts in the bone marrow decreased and the patient became transfusion-independent. Interestingly, levels of serum G-CSF showed a similar trend to the myeloid leukocytosis, while those of serum GM-CSF and IL-17 were undetectable throughout the clinical course, suggesting that a differentiation response to AZA treatment might lead to the myeloid leukemoid reaction. Our case implies that a marked but transient myeloid leukemoid reaction mimicking CMML progression can develop during AZA treatment, which requires careful clinical monitoring and differential diagnosis.

Phase I and II study of azacitidine in Japanese patients with myelodysplastic syndromes.

Azacitidine, an inhibitor of DNA methyltransferase, is reported to have antileukemic efficacy and is approved for the treatment of myelodysplastic syndromes in Western countries. We have conducted a Phase I/II study of azacitidine in Japanese patients with myelodysplastic syndromes to evaluate its pharmacokinetics, efficacy, and safety. In all, 53 patients received 75 mg/m(2) azacitidine subcutaneously or intravenously once daily for seven consecutive days on a 28-day cycle. The C(max) following intravenous administration was approximately 3.7-fold higher than that following subcutaneous administration, whereas the area under the plasma concentration-time curve from time zero to infinity was comparable for subcutaneous and intravenous administration. The bioavailability of azacitidine following subcutaneous administration was 91.1%, indicating that azacitidine is nearly completely absorbed after subcutaneous administration. The hematologic improvement and hematologic response rates were 54.9% (28/51) and 28.3% (15/53), respectively, and there were no differences between the two routes of administration. Azacitidine was generally well tolerated and clinically manageable in Japanese patients with myelodysplastic syndromes. Adverse events occurred in ≥ 20% of patients included hematologic toxicity, gastrointestinal events, and general disorders, such as malaise. Grade 3/4 adverse events that occurred in ≥ 50% of patients were all due to hematologic toxicity. The safety profile of azacitidine was generally similar for both routes of administration, with the exception of injection site reactions observed following subcutaneous administration. These results indicate that azacitidine can be expected to be a useful therapeutic agent in Japanese patients with myelodysplastic syndromes.

Eight-year follow-up of patients with immune thrombocytopenic purpura related toH. pyloriinfection.

Thrombocytopenia related to Helicobacter pylori infection is a definitive subset of chronic immune thrombocytopenic purpura (ITP) but its long-term prognosis has not been evaluated extensively. The possibility of recurrence of thrombocytopenia after re-infection of H. pylori is another concern. We evaluated 8-year follow-up data for 11 patients with ITP related to H. pylori infection in a single institution. In 2001, patients with chronic ITP were evaluated for H. pylori infection at the Tokyo Metropolitan Komagome Hospital using ¹³C urea breath test (UBIT). Nineteen patients turned out to be positive and were treated for H. pylori infection. Platelet count 6 months after treatment revealed complete response (CR) in 10 patients and response in one patient. Eight years later, 17 of these 19 patients were re-evaluated for H. pylori infection and platelet count. Platelet counts of the 11 previous responders remained to indicate CR. Two of 13 patients re-examined by UBIT showed positive results and one of these two patients continued to keep normal platelet count. Nonetheless, the prognosis of patients who responded to eradication was excellent.

Chronic kidney disease in long-term survivors of myeloablative allogeneic haematopoietic cell transplantation: prevalence and risk factors.

BACKGROUND: Chronic kidney disease (CKD) seems to be common in long-term survivors of haematopoietic cell transplantation (HCT). However, the range of its frequency is very wide, likely due to variability in the definitions of CKD and the periods of follow-up. METHODS: We conducted a cross-sectional and retrospective study in 158 adults who received myeloablative allogeneic HCT for lymphohaematologic malignancies at least 3 years ago and are alive today. The mean survival time was 6.15 +/- 4.88 years (range: 3-16 years). CKD was defined as a sustained decrease in glomerular filtration rate (GFR) or persistent proteinuria for a period more than 3 months. GFR was calculated based on serum creatinine (Cr) using the Modification of Diet in Renal Disease formula. Serum Cr and proteinuria were measured at least on three occasions separated by one or more months before the investigation. CKD was classified according to the National Kidney Foundation CKD staging. Proteinuria was defined as positive dipstick test > or =1+. The factors associated with the presence of CKD with a decrease of GFR (CKD > or = stage 3) were examined using multivariate logistic regression analysis, adjusted for demographic and clinical characteristics. RESULTS: The prevalence of proteinuria was found in 36 out of 158 patients (22.8%). The prevalence of each CKD stage was as follows: Stage 0 (no CKD), 98 patients (62.0%); Stage 1, 18 patients (11.4%); Stage 2, 15 patients (9.5%); Stage 3, 8 patients (5.1%); Stage 4, 10 patients (6.3%) and Stage 5, 9 patients (5.7%). Initiation of chronic dialysis treatment or transplant was performed in seven CKD stage-5 patients (4.4%) at a mean of 10.9 +/- 3.72 years after HCT. Multivariate analysis identified acute kidney injury with HCT [odds ratio (OR), 9.920; 95% confidence interval (CI), 2.084-39.68; P = 0.0051], hypertension after HCT (OR, 4.031; 95% CI, 1.044-13.06; P = 0.0346) and survival time after HCT (OR, 4.275; 95% CI, 2.823-23.04; P = 0.0481) as significant factors associated with the presence of CKD > or = stage 3. CONCLUSIONS: A remarkably high percentage of long-term survivors had evidence of proteinuria and all stages of CKD. CKD in transplant recipients may result from incomplete recovery from acute renal insults, hypertension and increasing longevity. The CKD cohort should be at a great risk for end-stage renal disease and cardiovascular morbidity and mortality. The burden of CKD should be recognized as a significant public health problem.

Erythrocytosis caused by erythropoietin-producing thymic carcinoma.

We describe the first reported case, in an 82-year-old man, of erythrocytosis caused by an erythropoietin (EPO)-producing thymic carcinoma. The patient underwent computed tomography-guided fine-needle aspiration of a 6-cm anterior mediastinal mass, and histological findings revealed thymic squamous cell carcinoma. The existence of EPO was confirmed immunohistochemically using the tumor tissue. Postoperative clinical improvement of erythrocytosis and the decline of EPO suggest a paraneoplastic nature of erythrocytosis as seen in this patient.

Possible association between obesity and posttransplantation complications including infectious diseases and acute graft-versus-host disease.

Both obesity and malnutrition are considered risk factors for complications after bone marrow transplantation (BMT). To elucidate the impact of pretransplantation body mass index (BMI) on clinical outcome, we performed a retrospective cohort study with registration data from the Japan Marrow Donor Program (JMDP). Between January 1998 and December 2005, a total of 3935 patients received unrelated BMT through the JMDP; of these, 3827 patients for whom pretransplantation height and weight data were available were included in the study. Patients were stratified according to pretransplantation BMI values (low BMI: BMI < 18 kg/m(2), n = 295; normal BMI: 18 < or = BMI < 25 kg/m(2), n = 2906; overweight: 25 < or = BMI <30 kg/m(2), n = 565; obese: 30 kg/m(2) < or = BMI, n = 61). In a univariate analysis, pretransplantation BMI was associated with a significantly greater risk of grade II-IV acute graft-versus-host disease (GVHD; P = .03). Multivariate analysis showed that pretransplantation BMI tended to be associated with an increased risk of grade II-IV acute GVHD (P = .07). Obesity was associated with an increased risk of infection compared with normal BMI (odds ratio = 1.9; 95% confidence interval = 1.1 to 3.2; P = .02). Our findings demonstrate a correlation between pretransplantation BMI and posttransplantation complications. Although BMI depends strongly on multiple factors, the effect of obesity on clinical outcome should be evaluated in a prospective study.

NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies.

BACKGROUND: NKG2D, an activating and co-stimulatory receptor expressed on natural killer cells and T cells, plays pivotal roles in immunity to microbial infections as well as in cancer immunosurveillance. This study examined the impact of donor and recipient polymorphisms in the NKG2D gene on the clinical outcomes of patients undergoing allogeneic T-cell-replete myeloablative bone marrow transplantation using an HLA-matched unrelated donor. DESIGN AND METHODS: The NKG2D polymorphism was retrospectively analyzed in a total 145 recipients with hematologic malignancies and their unrelated donors. The patients underwent transplantation following myeloablative conditioning; the recipients and donors were matched through the Japan Marrow Donor Program. RESULTS: In patients with standard-risk disease, the donor NKG2D-HNK1 haplotype, a haplotype expected to induce greater natural killer cell activity, was associated with significantly improved overall survival (adjusted hazard ratio, 0.44; 95% confidence interval, 0.23 to 0.85; p=0.01) as well as transplant related mortality (adjusted hazard ratio, 0.42; 95% confidence interval, 0.21 to 0.86; p=0.02), but had no impact on disease relapse or the development of grade II-IV acute graft-versus-host disease or chronic graft-versus-host disease. The NKG2D polymorphism did not significantly influence the transplant outcomes in patients with high-risk disease. CONCLUSIONS: These data suggest an association between the donor HNK1 haplotype and better clinical outcome among recipients, with standard-risk disease, of bone marrow transplants from HLA-matched unrelated donors.

Intracranial hemorrhage following allogeneic hematopoietic stem cell transplantation.

Charts and radiographs of 622 allogeneic hematopoietic stem cell transplant (HSCT) recipients, over a 20-year period, were retrospectively reviewed for intracranial hemorrhage (ICH) following transplant. A total of 21 cases of ICH were identified (3.4%) including 15 cases of intraparenchymal hemorrhage (IPH), two cases of subarachnoid hemorrhage (SAH), and four cases of subdural hematoma (SDH). The median time from transplantation to the onset of ICH was 63 days (range, 6-3,488 days). The clinical features of post-transplant ICH patients were similar and included hypertension, diabetes mellitus, chronic graft-versus-host disease (GVHD), systemic infection, and veno occlusive disease (VOD), recently referred to as sinusoidal obstruction syndrome, in addition to severe thrombocytopenia. Mortality rate was especially high (89%) after IPH with a median survival of 2 days (range, 0-148 days). In contrast, all patients with SAH or SDH following HSCT survived. The cause of post-transplant ICH appears to be multifactorial, including thrombocytopenia, hypertension, acute GVHD, VOD, and radiation therapy. Most patients in our series displayed severe thrombocytopenia at the onset of ICH, even though adequate prophylactic platelet transfusions were given. By univariate analysis, cord blood transplantation, acute GVHD, systemic infection, and VOD were related to the incidence of ICH, whereas prior CNS episodes and radiation therapy did not reach statistical significance. A multivariate analysis with logistic regression identified acute GVHD as the only factor that significantly influenced ICH occurrence.

Multiple myeloma with multiple and bulky extramedullary plasmacytomas as initial presentation.

We herein describe a rare case of multiple myeloma with an aggressive clinical course and the unusual manifestation of multiple organ involvement by plasma cells. A 58-year-old man noted difficulty in walking due to progressive swelling of his left lower limb. CT scan revealed a huge mass in the inguinal region in addition to masses located on the head, and in the aero-digestive tract and spinal canal. The pathological diagnosis of plasmacytoma was made on biopsied specimens of these masses, while plasma cells did not increase (5.8%) in aspirated bone marrow obtained at the same time. Serum IgG level was 6,387 mg/dl and immunoelectrophoresis demonstrated monoclonal IgG-kappa in the serum. Chemotherapy with vincristine, adriamycin, dexamethasone, subsequent high-dose cyclophosphamide, and irradiation involving both thoracic vertebral canal and inguinal regions resulted in improvement of initial symptoms. However, the patient relapsed soon after; new lesions developed in various parts of the body, including the left thigh and body trunk. Salvage therapy including bortezomib was no longer effective, and he eventually died 10 months after the initial diagnosis. Autopsy revealed the diffuse involvement of plasma cells of multiple organs, including the liver, spleen, abdominal lymph node, and bone marrow in addition to the left leg.

[Recent progress in the field of hematopoietic stem cell transplantation for leukemia].

The method and way of hematopoietic stem cell transplantation have been expanded and become complex recently. We discussed recent progress in this field, mainly in the treatment of leukemia. The first topic is the new arrival of the tyrosine kinase inhibitor, imatinib. Imatinib dramatically changed the treatment strategies for chronic myeloid leukemia. The same drug is now changing the treatment options and indications of hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Efforts have also been made to expand the cell source for transplantation to cord blood and haploidentical donors. Almost 5,000 patients have undergone cord blood transplantation in Japan. Finally, the results of reduced-intensity stem cell transplantation may well expand the patient population eligible for transplantation.

Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapy.

The clinical significance of minimal residual disease (MRD) is uncertain in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) treated with imatinib-combined chemotherapy. Here we report the results of prospective MRD monitoring in 100 adult patients. Three hundred and sixty-seven follow-up bone marrow samples, collected at predefined time points during a uniform treatment protocol, were analysed for BCR-ABL1 transcripts by quantitative reverse transcription polymerase chain reaction. Ninety-seven patients (97%) achieved complete remission (CR), and the relapse-free survival (RFS) rate was 46% at 3 years. Negative MRD at the end of induction therapy was not associated with longer RFS or a lower relapse rate (P = 0.800 and P = 0.964 respectively). Twenty-nine patients showed MRD elevation during haematological CR. Of these, 10 of the 16 who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) in first CR were alive without relapse at a median of 2.9 years after transplantation, whereas 12 of the 13 who had not undergone allogeneic HSCT experienced a relapse. These results demonstrate that, in Ph+ ALL patients treated with imatinib-combined chemotherapy, rapid molecular response is not associated with a favourable prognosis, and that a single observation of elevated MRD is predictive of subsequent relapse, but allogeneic HSCT can override its adverse effect.

Impact of AB0-blood group incompatibility on the outcome of recipients of bone marrow transplants from unrelated donors in the Japan Marrow Donor Program.

BACKGROUND: Although the AB0 blood group is one of two major antigen systems of relevance for transplantation in humans, there are still conflicting data concerning the influence of AB0 incompatibility on transplant outcome. This study investigated the effect of AB0 incompatibility in recipients of bone marrow transplants from unrelated donors. DESIGN AND METHODS: We retrospectively analyzed data from 5,549 patients who underwent bone marrow transplantation from unrelated donors in the Japan Marrow Donor Program. RESULTS: Overall survival rates in the group with major and minor mismatches were significantly lower than the rate in the AB0-identical group (AB0-identical 63.0%; major mismatch, 56.9%; minor mismatch, 57.1% at 1 year). Treatment-related mortality was higher in the major and minor mismatch groups, but there was no significant difference in the rate of relapse. Cox proportional hazards modeling showed that both major and minor AB0 incompatibility were significant risk factors for transplant-related mortality, independently of disease, patients' age, and HLA incompatibility. Delayed engraftment of neutrophils, platelets, and erythrocytes was observed in transplants with major incompatibility. There was a high incidence of grade 3 and 4 acute graft-versus-host disease in the groups with major and minor mismatches, which was caused by a high incidence of stage 2 to 4 liver graft-versus-host disease. Interestingly, the risk of grade 2 to 4 graft-versus-host disease in the major mismatch group was higher in patients with early engraftment of erythrocytes. Among the patients receiving reduced-intensity conditioning, the transplant-related mortality was also increased in AB0-incompatible transplants. CONCLUSIONS: Major and minor AB0 incompatibility have specific effects on transplant-related mortality and acute graft-versus-host disease in recipients of bone marrow transplants from unrelated donors.