Search

Mogamulizumab (MOG), a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, has recently played an important role in the treatment of adult T cell leukemia/lymphoma (ATLL). Because CCR4 is expressed on normal regulatory T cells as well as on ATLL cells, MOG may accelerate graft-versus-host disease (GVHD) by eradicating regulatory T cells in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is limited information about its safety and efficacy in patients treated with MOG before allo-HSCT. In the present study, 25 patients with ATLL were treated with MOG before allo-HSCT, after which 18 patients (72%) achieved remission. The overall survival and progression-free survival at 1 year post-transplantation were 20.2% (95% CI, 6.0% to 40.3%) and 15.0% (95% CI, 4.3% to 32.0%), respectively. The cumulative incidence of acute GVHD was 64.0% (95% CI, 40.7% to 80.1%) for grade II-IV and 34.7% (95% CI, 15.8% to 54.4%) for grade III-IV. The cumulative incidence of transplantation-related mortality (TRM) was 49.0% (95% CI, 27.0% to 67.8%). Six of 7 patients with acute GVHD grade III-IV died from GVHD, which was the leading cause of death. In particular, a shorter interval from the last administration of MOG to allo-HSCT was associated with more severe GVHD. MOG use before allo-HSCT may decrease the ATLL burden; however, it is associated with an increase in TRM due to severe GVHD. Because MOG is a potent anti-ATLL agent, new treatment protocols should be developed to integrate MOG at suitable doses and timing of administration to minimize unwanted GVHD development. [ABSTRACT FROM AUTHOR]

Study Objective To evaluate the efficacy and safety of aprepitant added to standard antiemetic regimens used in high-dose chemotherapy for allogeneic hematopoietic stem cell transplantation (allo- HSCT). Design Retrospective medical record review. Setting Hematology ward of a university hospital in Japan. Patients Of 88 patients treated with high-dose chemotherapy followed by allo- HSCT, 46 received aprepitant and granisetron as antiemetic therapy (between April 1, 2010, and December 31, 2011), and 42 received granisetron alone (between April 1, 2008, and March 31, 2010). Interventions Patients in both groups received 3 mg of granisetron intravenously 30 minutes before the administration of anticancer drugs. In the aprepitant group, 125 mg of aprepitant was administered orally 60-90 minutes before the administration of the first moderately to highly emetogenic anticancer drug. On the following days, 80 mg of aprepitant was administered orally every morning. The mean administration duration of aprepitant was 3.3 days (range 3-6 days). Measurements and Main Results The primary objective was to evaluate the percentage of patients who achieved complete response ( CR; no vomiting and none to mild nausea). The CR rate in the aprepitant group was significantly higher than that in the control group (48% vs 24%, p=0.02). Multivariate analysis showed that nonprophylactic use of aprepitant was associated with failure to achieve CR (odds ratio [ OR] 2.92; 95% confidence interval [ CI] 1.13-7.99, p=0.03). The frequency of abdominal pain was lower in the aprepitant group (9% vs 25%, p=0.03). Rates of other frequently observed adverse drug events were similar between groups. There was no significant difference in neutrophil engraftment (median 18 vs 17 days), platelet engraftment (median 32 vs 32 days), the incidence of acute graft-versus-host-disease (63% vs 55%, p=0.52), viral infection (74% vs 67%, p=0.49), or 1-year overall survival (63% vs 62%, p=0.90) between the two groups. Conclusions The addition of aprepitant to granisetron increases the antiemetic effect without influencing transplantation-related toxicities in allo- HSCT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Highlights • HHV6-associated myelitis (2.5%) and CIPS (1.8%) were rarely documented in 435 HSCT recipients. • These 2 diseases had similar sensory-related symptoms, such as pruritus and severe pain. • Diagnostic images did not provide definite evidence specific for each disease. • HHV6 encephalitis/myelitis but not CIPS was associated with poor overall survival. • Detection of HHV6 is crucial for differential diagnoses and immediate treatment of the 2 diseases. Abstract Human herpes virus-6 (HHV6)-associated myelitis and calcineurin inhibitor–induced pain syndrome (CIPS) are serious complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because these 2 complications cause similar sensory nerve–related symptoms, such as paresthesia, pruritus, and severe pain occurring around the engraftment, it can be difficult to differentially diagnose the 2 conditions. We retrospectively analyzed 435 recipients to distinguish clinical symptoms of these 2 complications. Twenty-four patients (5.5%) developed HHV6-associated encephalitis/myelitis; of these, 11 (2.5%) presented only with myelitis-related symptoms (HHV6-associated myelitis), which was confirmed by the detection of HHV6 DNA, and 8 (1.8%) had CIPS, with undetected HHV6 DNA. All patients with HHV6-associated myelitis or CIPS exhibited similar sensory nerve–related symptoms. Diagnostic images did not provide definite evidence specific for each disease. Symptoms of all patients with CIPS improved after switching to another immunosuppressant. Overall survival rate at 2 years for patients with HHV6-associated encephalitis/myelitis was significantly lower than that of CIPS (13.1% versus 29.2%; P =.049) or that of patients without HHV6-associated encephalitis/myelitis or CIPS (42.4%; P =.036), whereas there was no significant difference among the latter 2 groups (P =.889). The development of HHV6-associated encephalitis/myelitis but not CIPS was significantly associated with poor prognosis. Thus, transplant physicians should be aware that sensory nerve–related symptoms indicate early manifestations that might be correlated with reactivation of HHV6 or CIPS. Therefore, identification of HHV6 DNA is crucial for making a differential diagnosis and immediately starting appropriate treatments for each complication. [ABSTRACT FROM AUTHOR]

Pneumococcal diseases are one of the most important infectious complications in the late period following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The importance of long-term follow-up care is increasing, as the number of long-term survivors following allo-HSCT increases, but there has been a dearth of research specifically focusing on pneumococcal diseases during the late post-transplant period (day >100). Using a transplant registry database between January 1, 2001 and December 31, 2011, we aimed to assess the clinical spectrum and risk factors for pneumococcal diseases in the late post-transplant period. Among the 22,514 recipients who received allo-HSCT over an 11-year period and could be followed for ≥100 days, 43 patients developed 49 episodes of pneumococcal diseases. Six of the 43 patients died from pneumococcal diseases, and four of these six patients died within a week, despite having undergone allo-HSCT two or more years ago. A history of chronic graft-versus-host disease (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.15–4.66; P = 0.02), viral infection (OR, 3.38; 95% CI, 1.70–6.72; P < 0.01), and complete remission of the underlying disease at the time of transplantation (OR, 2.38; 95%CI, 1.10–5.14; P = 0.03) were identified as risk factors. Given the risk of sudden death and the high mortality rate, attention should be paid to pneumococcal diseases in providing long-term follow-up care, even several years after allo-HSCT. [ABSTRACT FROM AUTHOR]

Summary: Allogeneic haematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for some patients with acute myeloid leukaemia (AML) who are refractory to chemotherapy. Cord blood transplantation (CBT) is a reasonable option in such cases because of its rapid availability. Recently, a growing number of human leucocyte antigen (HLA)‐haploidentical related donor HSCTs (haplo‐HSCTs) have been performed, although its effectiveness remains undetermined. Using the Japanese nationwide transplantation registry data, we identified 2438 patients aged ≥16 years who received CBT or haplo‐HSCT as their first transplant for non‐remission AML between January 2008 and December 2018. After 2:1 propensity score matching, 918 patients in the CBT group and 459 patients in the haplo‐HSCT group were selected. In this matched cohort, no significant difference in overall survival (OS) was observed between the CBT and haplo‐HSCT groups (hazard ratio [HR] of haplo‐HSCT to CBT 1.02, 95% confidence interval [CI] 0.89–1.16). Similarly, no significant difference in the cumulative incidence of relapse (HR 1.09, 95% CI 0.93–1.28) or non‐relapse mortality (HR 0.94, 95% CI 0.76–1.18). Subgroup analysis showed that CBT was significantly associated with preferable OS in patients receiving myeloablative conditioning. Our data showed comparable outcomes between haplo‐HSCT and CBT recipients with non‐remission AML. [ABSTRACT FROM AUTHOR]

Purpose: Hematopoietic cell transplantation (HCT) is a curative therapy for most patients with inborn errors of immunity (IEI). We conducted a nationwide study on HCT for patients with IEI other than severe combined immunodeficiency (non-SCID) in Japan. Methods: Data from the Japanese national database (Transplant Registry Unified Management Program, TRUMP) for 566 patients with non-SCID IEI, who underwent their first HCT between 1985 and 2016, were retrospectively analyzed. Results: The 10-year overall survival (OS) and event-free survival (EFS) were 74% and 64%, respectively. The 10-year OS for HCT from unrelated bone marrow (URBM), accounting for 39% of HCTs, was comparable to that for HCT from matched sibling donor (MSD), 79% and 81%, respectively. HCT from unrelated cord blood (URCB), accounting for 28% of HCTs, was also common, with a 10-year OS of 69% but less robust engraftment. The intensity of conditioning was not associated with OS or neutrophil recovery; however, myeloablative conditioning was more frequently associated with infection-related death. Patients who received myeloablative irradiation showed poor OS. Multivariate analyses revealed that HCT in 1985–1995 (hazard ratio [HR], 2.0; P = 0.03), URCB (HR, 2.0; P = 0.01), and related donor other than MSD (ORD) (HR, 2.9; P < 0.001) were associated with poor OS, and URCB (HR, 3.6; P < 0.001) and ORD (HR, 2.7; P = 0.02) showed a higher incidence of retransplantation. Conclusions: We present the 1985–2016 status of HCT for non-SCID IEI in Japan with sufficient statistical power, highlighting the potential of URBM as an alternative donor and the feasibility of reduced intensity conditioning. [ABSTRACT FROM AUTHOR]

Abstract: Allogeneic hematopoietic cell transplantation (HCT), but not autologous HCT, can provide long-term remission in some patients with adult T cell leukemia-lymphoma (ATL). We retrospectively analyzed the effects of acute graft-versus-host disease (GVHD) among the 616 patients with ATL who survived at least 30 days after allogeneic HCT with other than cord blood grafts. Multivariate analyses treating the occurrence of GVHD as a time-varying covariate demonstrated an association between grade I-II acute GVHD and favorable overall survival (OS) (hazard ratio [HR], 0.634; 95% confidence interval [CI], 0.477 to 0.843), whereas grade III-IV acute GVHD showed a trend toward unfavorable OS (HR, 1.380; 95% CI, 0.988 to 1.927) compared with nonacute GVHD. In subsequent multivariate analyses of patients who survived at least 100 days after HCT (n = 431), the presence of limited chronic GVHD showed a trend toward favorable OS (HR, 0.597; 95% CI, 0.354 to 1.007), and extensive chronic GVHD had a significant effect on OS (HR, 0.585; 95% CI, 0.389 to 0.880). There were no significant interactions between myeloablative conditioning or reduced-intensity conditioning with OS even when acute GVHD was absent or present at grade I-II or grade III-IV or when chronic GVHD was absent, limited, or extensive. This study demonstrates the actual existence of graft-versus-ATL effects in patients with ATL regardless of whether myeloablative conditioning or reduced-intensity conditioning is used. [Copyright &y& Elsevier]

Purpose: Hematopoietic cell transplantation (HCT) is a curative therapy for patients with severe combined immunodeficiency (SCID). Here, we conducted a nationwide study to assess the outcome of SCID patients after HCT in Japan. Methods: A cohort of 181 SCID patients undergoing their first allogeneic HCT in 1974–2016 was studied by using the Japanese national database (Transplant Registry Unified Management Program, TRUMP). Results: The 10-year overall survival (OS) of the patients who received HCT in 2006–2016 was 67%. Umbilical cord blood (UCB) transplantation was performed in 81 patients (45%). The outcomes of HCT from HLA-matched UCB (n = 21) and matched sibling donors (n = 22) were comparable, including 10-year OS (91% vs. 91%), neutrophil recovery (cumulative incidence at 30 days, 89% vs. 100%), and platelet recovery (cumulative incidence at 60 days, 89% vs. 100%). Multivariate analysis of the patients who received HCT in 2006–2016 demonstrated that the following factors were associated with poor OS: bacterial or fungal infection at HCT (hazard ratio (HR): 3.8, P = 0.006), cytomegalovirus infection prior to HCT (HR: 9.4, P = 0.03), ≥ 4 months of age at HCT (HR: 25.5, P = 0.009), and mismatched UCB (HR: 19.8, P = 0.01). Conclusion: We showed the potential of HLA-matched UCB as a donor source with higher priority for SCID patients. We also demonstrated that early age at HCT without active infection is critical for a better prognosis, highlighting the importance of newborn screening for SCID. [ABSTRACT FROM AUTHOR]

Adult T-cell leukemia-lymphoma (ATL) is an intractable mature T-cell neoplasm. We performed a nationwide retrospective study of allogeneic hematopoietic stem cell transplantation (HSCT) for ATL in Japan, with special emphasis on the ef-fects of the preconditioning regimen. This is the largest study of ATL patients receiv-ing HSCT. Median overall survival (OS) and 3-year OS of bone marrow or periph-eral blood transplantation recipients (n = 586) was 9.9 months (95% confidence interval, 7.4-13.2 months) and 36% (32%-41%), respectively. These values for recipients of myeloablative conditioning (MAC; n = 280) and reduced intensity con-ditioning (RIC; n = 306) were 9.5 months (6.7-18.0 months) and 39% (33%-45%) and 10.0 months (7.2-14.0 months) and 34% (29%-40%), respectively. Multivariate anal-ysis demonstrated 5 significant variables contributing to poorer OS, namely, older age, male sex, not in complete remission, poor performance status, and transplantation from unrelated donors. Although no significant difference in OS between MAC and RIC was observed, there was a trend indicating that RIC contributed to better OS in older patients. Regarding mortality, RIC was significantly associated with ATL-related mortality compared with MAC. In conclusion, allogeneic HSCT not only with MAC but also with RIC is an effective treatment resulting in long-term survival in selected patients with ATL. [ABSTRACT FROM AUTHOR]

As a source for hematopoietic stem cell transplantation (HSCT), cord blood transplantation from unrelated donors (UCBT) is now considered as an acceptable alternative to patients who need unrelated HSCT. To confirm the findings that mismatched UCBT is feasible, we discussed here the results for 477 patients with hematologic malignancies and non-malignancies who were subjected to UCBT coordinated by the Japanese Cord Blood Bank Network (JCBBN). From February 1997 to October 2001, 411 patients with malignancies and 66 with non-malignancies had UCBT through the cord blood bank in the JCBBN; 311 patients had HLA 0-1 mismatched UCBT; 165, had a 2-4 HLA mismatch. The Kaplan-Meier estimates for 3-year disease-free survival rate (DFS) were 35.2 ± 2.8% in malignant diseases, and 33.6 ± 7.2% in patients with non-malignant diseases. The HLA disparity had no effect on DFS, incidence of acute graft-versus-host disease, or engraftment. As reported previously, we also noted the importance of graft cell dose in determining survival in UCBT. Major advantages of UCBT include its rapid availability compared with unrelated donor bone marrow, and tolerance of an HLA mismatch at 2 loci, which will enable extension of the donor pool. This review outlines the latest UCBT progress, with emphasis on practical considerations in HLA-mismatched umbilical cord blood selection. [ABSTRACT FROM AUTHOR]

Lysosomal storage disorders and peroxisomal disorders are rare diseases caused by the accumulation of substrates of the metabolic pathway within lysosomes and peroxisomes, respectively. Owing to the rarity of these diseases, the prevalence of lysosomal storage disorders and peroxisomal disorders in Japan is unknown. Therefore, we conducted a nationwide survey to estimate the number of patients with lysosomal storage disorders and peroxisomal disorders in Japan. A nationwide survey was conducted following the "Manual of nationwide epidemiological survey for understanding patient number and clinical epidemiology of rare diseases (3rd version)". A questionnaire asking for detailed information, such as disease phenotypes and medical history, was created and sent to 504 institutions with doctors who have experience in treating patients with lysosomal storage disorders and peroxisomal disorders. Result A total of 303 completed questionnaires were collected from 504 institutions (response rate: 60.1%). The number of patients was estimated by calculating the rate/frequency of overlap. The estimated number of patients was 1658 (±264.8) for Fabry disease, 72 (±11.3) for mucopolysaccharidosis I, 275 (±49.9) for mucopolysaccharidosis II, 211 (±31.3) for Gaucher disease, 124 (±25.8) for Pompe disease, 83 (±44.3) for metachromatic leukodystrophy, 57 (±9.4) for Niemann-Pick type C, and 262 (±42.3) for adrenoleukodystrophy. In addition the birth prevalence was calculated using the estimated number of patients and birth year data for each disease, and was 1.25 for Fabry disease, 0.09 for mucopolysaccharidosis I, 0.38 for mucopolysaccharidosis II, 0.19 for Gaucher disease, 0.14 for Pompe disease, 0.16 for metachromatic leukodystrophy, 0.16 for Niemann-Pick type C, and 0.20 for adrenoleukodystrophy. Among the diseases analyzed, the disease with the highest prevalence was Fabry disease, followed by mucopolysaccharidosis II, adrenoleukodystrophy, Gaucher disease and metachromatic leukodystrophy. In particular, the high prevalence of mucopolysaccharidosis II and Gaucher disease type II was a feature characteristic of Japan. We estimated the number of patients with lysosomal storage disorders and peroxisomal disorders in Japan. The details of the age at diagnosis and treatment methods for each disease were clarified, and will be useful for the early diagnosis of these patients and to provide appropriate treatments. Furthermore, our results suggest that supportive care and the development of an environment that can provide optimal medical care is important in the future. [ABSTRACT FROM AUTHOR]

• Hematopoietic cell transplantation is the only curative therapy for juvenile myelomonocytic leukemia. • Busulfan/fludarabine/melphalan seems to offer the best chance of long-term survival. • Chronic graft-versus-host disease correlates with improved survival by reducing relapse. • Treatment strategies enhancing graft-versus-leukemia effects may further improve outcome. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for juvenile myelomonocytic leukemia (JMML), but few large studies of HSCT for JMML exist. Using data from the Japan Society for Hematopoietic Cell Transplantation registry, we analyzed the outcomes of 129 children with JMML who underwent HSCT between 2000 and 2011. The 5-year overall survival (OS) rate and cumulative incidence of relapse were 64% and 34%, respectively. A regimen of busulfan/fludarabine/melphalan was the most commonly used (59 patients) and provided the best outcomes; the 5-year OS rate reached 73%, and the cumulative incidences of relapse and transplantation-related mortality were 26% and 9%, respectively. In contrast, the use of the irradiation-based myeloablative regimen was the most significant risk factor for OS (hazard ratio [HR], 2.92; P =.004) in the multivariate model. In addition, chronic graft-versus-host disease (GVHD) was strongly associated with lower relapse (HR, 0.37; P =.029) and favorable survival (HR, 0.22; P =.006). The current study has shown that a significant proportion of children with JMML can be cured with HSCT, especially those receiving the busulfan/fludarabine/melphalan regimen. Based on the lower relapse and better survival observed in patients with chronic GVHD, additional treatment strategies that focus on enhancing graft-versus-leukemia effects may further improve survival. [ABSTRACT FROM AUTHOR]

• We assessed the effect of donor human T cell leukemia virus 1 serostatus on outcomes of allogeneic hematopoietic stem cell transplantation (allo-HCT) in adult T cell leukemia-lymphoma. • There was no significant difference in overall survival or incidence of mortality. • This might aid the choice of appropriate and timely alternative donors for allo-HCT. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only available curative treatment option for patients with aggressive adult T cell leukemia-lymphoma (ATL). Donor human T cell leukemia virus (HTLV) 1 seropositivity is a critical concern when choosing relative donors, as they are not usually recommended due solely to the occurrence of donor-derived ATL. A previous report suggested that allo-HCT with an HTLV-1-seropositive donor increased ATL-related mortality. We updated the risk assessment for choosing an HTLV-1-seropositive allo-HCT donor for ATL. Our current registry data, which include larger numbers of HTLV-1-seropositive donors and longer observation periods, revealed no significant difference in overall survival (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.70-1.24; P =.61) or cumulative incidence of either ATL-related (HR, 0.96; 95% CI, 0.64 to 1.45; P =.80) or non-ATL-related mortality (HR, 0.91; 95% CI, 0.61 to 1.37; P =.66). Similarly, when considering only patients with ATL in complete remission, there was no significant difference in overall survival (HR, 1.02; 95% CI, 0.70 to 1.49; P =.91) or cumulative incidence of either ATL-related (HR, 1.20; 95% CI, 0.66 to 2.20; P=0.54) or non-ATL-related mortality (HR, 0.86; 95% CI, 0.52-1.42; P =.66). These data indicate that selecting HTLV-1-seropositive donors might not be contraindicated for patients with ATL receiving allo-HCT if alternative donors are unavailable. Further risk assessment remains to be performed. [ABSTRACT FROM AUTHOR]

• Hematopoietic stem cell transplantation (HSCT) recipients exhibited low seropositivity for measles, rubella, mumps, and varicella zoster virus. • History of chronic graft-versus-host disease (GVHD) was associated with a high seropositivity rate for measles. • Nineteen of 32 HSCT recipients seronegative for measles became seropositive after vaccination. • Thirty percent of 20 HSCT recipients seronegative for rubella became seropositive after vaccination. • History of cGVHD was associated with seroconversion after vaccination. Vaccination against vaccine-preventable diseases (VPDs) is highly recommended for hematopoietic stem cell transplantation (HSCT) recipients by several guidelines; however, the safety and seropositivity after live attenuated vaccines remain unclear in adult HSCT recipients. We analyzed titers of antibodies against measles, rubella, mumps, and varicella zoster virus (VZV) from Japanese adult patients who underwent allogeneic HSCT (allo-HSCT) (n = 74), autologous HSCT (auto-HSCT) (n = 39), or chemotherapy (n = 93). The seropositive rates for measles, rubella, mumps, and VZV in allo-HSCT recipients were 20.2%, 36.4%, 5.4%, and 55.4%, respectively. These rates were equivalent to those in auto-HSCT recipients but were significantly lower than those in patients receiving chemotherapy. Antibody titers tended to gradually decrease with time. Twenty-nine allo-HSCT recipients and 8 auto-HSCT recipients received live attenuated vaccines against VPDs for which they tested seronegative. The titers of antibodies against measles, rubella, and mumps significantly increased after 2 shots of vaccine, and the seropositive rate increased up to 19%, 30%, and 27%, respectively. Three patients (8.1%) experienced mild adverse events, which resolved promptly, indicating safe administration of the live attenuated vaccines. In multivariate analysis, history of chronic graft-versus-host disease was significantly associated with high seropositivity for measles as well as high seroconversion rate for measles after vaccination. Live attenuated vaccines against VPDs were safely administered in seronegative adult HSCT recipients. A further observational study is crucial to evaluate the efficacy of vaccination in seronegative HSCT patients. [ABSTRACT FROM AUTHOR]

Highlights • Bloodstream infection was documented in 13.6% of allogeneic transplant recipients. • Enteric bacteria/fungi were major (58%) causes of this infectious complication. • Bloodstream infection correlated with gastrointestinal graft-versus-host disease. • Patients with bloodstream infection showed an inferior prognosis. Abstract Bloodstream infection (BSI) is a well-known cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Here, we conducted a retrospective study to assess the morbidity, etiology, risk factors, and outcomes of BSI in the postengraftment period (PE-BSI) after allo-HSCT. Forty-three of 316 patients (13.6%) developed 57 PE-BSI episodes, in which 62 pathogens were isolated: Gram-positive bacteria, gram-negative bacteria, and fungi, respectively, accounted for 54.8%, 35.5%, and 9.7% of the isolates. Multivariate analysis revealed methylprednisolone use for graft-versus-host disease (GVHD) prophylaxis (odds ratio [OR], 6.49; 95% confidence interval [CI], 1.49 to 28.2; P =.013) and acute gastrointestinal GVHD (GI-GVHD) (OR, 8.82; 95% CI, 3.99 to 19.5; P <.0001) as risk factors for developing PE-BSI. This finding suggested that GI-GVHD increases the risk of bacterial translocation and subsequent septicemia. Moreover, among patients with GI-GVHD, insufficient response to corticosteroids, presumably related to an intestinal dysbiosis, significantly correlated with this complication. Patients with PE-BSI presented worse outcome compared with those without (3-year overall survival, 47.0% versus 18.6%; P <.001). Close microbiologic monitoring for BSIs and minimizing intestinal dysbiosis may be crucial to break the vicious cycle between GI-GVHD and bacteremia and to improve transplant outcomes especially in patients who require additional immunosuppressants. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic option for patients with chronic myelomonocytic leukemia (CMML). We retrospectively compared the post-transplantation outcomes of 159 patients with CMML who underwent allo-HSCT using 4 types of donor sources: HLA-matched related donor graft, unrelated bone marrow (U-BM), unrelated cord blood (U-CB), and HLA-mismatched related donor graft. The median patient age at allo-HSCT was 54 years (range, 16 to 75 years). In multivariate analyses, the use of HLA-matched related donor grafts correlated with better overall survival than U-BM (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.21 to 3.48; P  = .008), U-CB (HR, 3.80; 95% CI, 2.07 to 6.95; P  < .001), or HLA-mismatched related donor grafts (HR, 6.18; 95% CI, 2.70 to 14.15; P  < .001). Mortality after the relapse or progression of CMML did not significantly differ among the 4 types of donor source. Transplantation-related mortality was highest in recipients of U-CB (HR, 3.32; 95% CI, 1.33 to 8.26; P  = .010). In patients with CMML, allo-HSCT using an alternative donor may contribute to durable remission; however, further improvements in transplantation-related mortality are required for this type of transplantation. [ABSTRACT FROM AUTHOR]

In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT), post-transplant lung infection is critical for their prognosis. Mycobacterium abscessus complex is not fully recognized as a nontuberculous mycobacteria (NTM) pathogen of post-SCT lung infection. Here, we present three post-allogeneic SCT patients who developed pulmonary infection caused by M. abscessus complex including M. abscessus and M. massiliense . In all three cases, macrolide antibiotics had been administered for bronchiolitis obliterans syndrome (BOS) before the confirmation of their infection, and macrolide resistance was noted in the M. abscessus isolates, one of which resulted in an unfavorable treatment outcome. It is important to consider M. abscessus lung infection as well as other NTM in patients receiving allo-SCT, particularly those receiving macrolide therapy for BOS. [ABSTRACT FROM AUTHOR]

Graft failure (GF) is the most critical life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia, for which a second transplantation is the only effective treatment. Optimal procedures have not been established for the second transplantation in this setting, however. Here we retrospectively analyzed the outcomes of 22 patients with aplastic anemia, age ≥16 years, who underwent umbilical cord blood transplantation for GF after the first HSCT using the registry database of the Japan Society for Hematopoietic Cell Transplantation. The median age of patients was 36 years (range, 16 to 72 years), and the median time from the first to the second transplant was 77 days (range, 29 to 1061 days). The cumulative incidence of neutrophil engraftment at day 60 post-transplantation was 45.5% (95% confidence interval [CI], 23.6% to 65.0%). With a median follow-up of 50 months, the 4-year overall survival (OS) was 38.5% (95% CI, 18.4% to 58.5%). Mycofenolate mofetil–based graft-versus-host disease prophylaxis demonstrated greater neutrophil recovery than prophylaxis with calcineurin inhibitor alone or methotrexate-based prophylaxis (66.7% versus 37.5%; P  = .04). The use of such conditioning regimens as fludarabine + melphalan or cyclophosphamide + low-dose total body irradiation was associated with better engraftment (58.3% versus 30%; P  = .05) and better 4-year OS (55.6% versus 20%; P  = .05) than other regimens. Although further investigation is needed, umbilical cord blood could be an effective and promising option for stem cell source for urgent second transplantation in patients with aplastic anemia who develop GF after the first HSCT. [ABSTRACT FROM AUTHOR]

Few reports have focused on adolescent and young adult (AYA) patients with acute myeloid leukemia (AML) treated with hematopoietic stem cell transplantation (HSCT). We performed a retrospective analysis based on data obtained from a Japanese nationwide registration database to compare HSCT outcomes in AYA patients with AML with those in children with AML. An analysis of the 2973 patients with de novo AML who received allogeneic HSCT from 1990 to 2013 showed inferior 5-year overall survival (OS) (54% versus 58%, P  <   .01) and increased treatment-related mortality (TRM) (16% versus 13%, P  = .02) in AYA patients. Multivariate analysis for both OS and TRM showed a significant negative impact on AYAs. However, the negative impact of older age lost its significance in an additional analysis focusing on 1407 recent transplant recipients with high-resolution HLA typing (2000 to 2013). Finally, we analyzed the impact of transplantation center type on HSCT outcomes in 317 adolescent patients (15 to 18 years old) and found no difference in outcomes between patients treated at a pediatric or an adult hospital. Higher age was a strong predictive factor for inferior OS resulting from increased TRM, which can be eliminated with better donor selection using high-resolution HLA typing. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the best therapeutic option for childhood high-risk acute leukemia. However, which donor source is optimal for children lacking an identical sibling remains unclear. To evaluate the clinical impact of donor source on allo-HSCT in childhood acute leukemia, we analyzed data from 577 children who underwent allo-HSCT after a myeloablative regimen during first or second complete remission from 2005 to 2012, using registry data of the Japan Society for Hematopoietic Cell Transplantation, and we compared outcomes of 7/8 to 8/8 HLA allelic–matched unrelated bone marrow transplantation (UR-BMT, n = 218) and 4/6 to 6/6 HLA allelic–matched unrelated cord blood transplantation (UR-CBT, n = 200) to those of HLA-identical related bone marrow transplantation (ID-BMT, n = 159). The median follow-up of survivors was 40.0 months. Three-year overall survival (OS) and leukemia-free survival (LFS) rates for ID-BMT, UR-BMT, and UR-CBT were 74.8% and 69.0%, 75.0% and 69.6%, and 71.8% and 63.8%, respectively. The multivariate analysis demonstrated that OS and LFS for the 3 groups are comparable, although UR-CBT carries a greater risk of nonrelapse mortality (hazard ratio, 2.20; P  = .03, compared to ID-BMT) in the myeloablative setting for childhood high-risk acute leukemia. [ABSTRACT FROM AUTHOR]

Autologous hematopoietic stem cell transplantation (auto-HCT) is considered a standard therapy for transplant-eligible patients with multiple myeloma, while allogeneic HCT (allo-HCT) is controversial. We retrospectively analyzed 765 patients with myeloma who underwent tandem transplantation between 1998 and 2012 using Japanese registry data. We evaluated the clinical outcomes of tandem auto-HCT (n = 676) and auto/allo-HCT (n = 89). To adjust for a selection bias, we compared overall survival (OS) between the two groups by a propensity score analysis. The probability of OS at six years was 58.5% for the tandem auto-HCT group and 54.4% for the tandem auto/allo-HCT group (p = 0.47). In a matched-pair analysis based on the propensity score, the difference in survival between the two groups was not statistically significant, although the survival curve appeared to reach a plateau beyond five years in the auto/allo group. Further strategies to reduce treatment-related mortality and enhance a graft-versus-myeloma effect are necessary to improve OS. [ABSTRACT FROM AUTHOR]

The article presents a study which analyzed autologous stem cell transplantation (ASCT) recipients with hematological disorders hospitalized between January 2005 and March 2007. Topics discussed include the clinical characteristics of the patients, number of patients who developed engraftment syndrome (ES), and the high incidence of ES after ASCT in patients with POEMS syndrome.

Bone marrow (BM) is the preferred graft source for hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) compared with mobilized peripheral blood stem cells (PBSCs). We hypothesized that this recommendation may not apply to those regions where patients present later in their disease course, with heavier transfusion load and with higher graft failure rates. Patients with SAA who received HSCT from an HLA-matched sibling donor from 1995 to 2009 and reported to the Center for International Blood and Marrow Transplant Research or the Japan Society for Hematopoietic Cell Transplantation were analyzed. The study population was categorized by gross national income per capita and region/countries into 4 groups. Groups analyzed were high-income countries (HIC), which were further divided into United States–Canada (n = 486) and other HIC (n = 1264); upper middle income (UMIC) (n = 482); and combined lower-middle, low-income countries (LM-LIC) (n = 142). In multivariate analysis, overall survival (OS) was highest with BM as graft source in HIC compared with PBSCs in all countries or BM in UMIC or LM-LIC ( P < .001). There was no significant difference in OS between BM and PBSCs in UMIC ( P = .32) or LM-LIC ( P = .23). In LM-LIC the 28-day neutrophil engraftment was higher with PBSCs compared with BM (97% versus 77%, P = .002). Chronic graft-versus-host disease was significantly higher with PBSCs in all groups. Whereas BM should definitely be the preferred graft source for HLA-matched sibling HSCT in SAA, PBSCs may be an acceptable alternative in countries with limited resources when treating patients at high risk of graft failure and infective complications. [ABSTRACT FROM AUTHOR]

A total of 216 patients with IEM were treated by allogeneic HSCT in Japan from 1985 until 2010. The results of UCBT have improved, and the OS rate of UCBT (81.9%) was not different from those of RBMT (87.2%) or UBMT (73.9%) in 2000-2010. However, EFS rates in RBMT (73.2%) and UBMT (62.2%) were better than that in UCBT (49.5%), and the difference between RBMT and UCBT was significant (p = 0.01). The EFS rate of patients conditioned by RIC (74.6%) was comparable or slightly better than in those who underwent MAC with irradiation (57.9%) or without irradiation (54.2%) in 2000-2010. A more pronounced trend was observed toward differential EFS for UCBT in 2000-2010: RIC (62.9%), MAC with irradiation (20.0%), and MAC without irradiation (42.1%). The difference between RIC and MAC with irradiation was significant (p < 0.03). In summary, we report a Japanese registry analysis of HSCT for IEM with improving survival in UCBT. The introduction of RIC after 2000 was considered to contribute to this improvement. UCBT could be recommended for those who lack an HLA-identical sibling donor. [ABSTRACT FROM AUTHOR]

Pediatric patients with acute myeloid leukemia (AML) mainly receive myeloablative conditioning regimens based on busulfan (BU) or total body irradiation (TBI) before allogeneic hematopoietic cell transplantation (allo-HCT); however, the optimal conditioning regimen remains unclear. To identify which of these regimens is better for pediatric patients, we performed a retrospective analysis of nationwide registration data collected in Japan between 2006 and 2011 to assess the outcomes of patients receiving these regimens before a first allo-HCT. Myeloablative conditioning regimens based on i.v. BU (i.v. BU-MAC) (n = 69) or TBI (TBI-MAC) (n = 151) were compared in pediatric AML patients in first or second complete remission (CR1/CR2). The incidences of sinusoid obstruction syndrome, acute and chronic graft-versus-host disease, and early nonrelapse mortality (NRM) before day 100 were similar for both conditioning groups; however, the incidence of bacterial infection during the acute period was higher in the TBI-MAC group ( P = .008). Both groups showed a similar incidence of NRM, and there was no significant difference in the incidence of relapse between the groups. Univariate and multivariate analyses revealed no significant differences in the 2-year relapse-free survival rates for the i.v. BU-MAC and TBI-MAC groups in the CR1/CR2 setting (71% versus 67%, P = .36; hazard ratio, .73; 95% CI, .43 to 1.24, respectively). TBI-MAC was no better than i.v. BU-MAC for pediatric AML patients in remission. Although this retrospective registry-based analysis has several limitations, i.v. BU-MAC warrants further evaluation in a prospective trial. [ABSTRACT FROM AUTHOR]

Cord blood has been investigated as an alternative source for hematopoietic stem cell transplantation, but information about its use for multiple myeloma is limited. The purpose of this study was to evaluate the feasibility of cord blood transplantation (CBT) for patients with multiple myeloma. Eighty-six patients with multiple myeloma who underwent a first CBT between 2001 and 2011 were included in this retrospective study. Sixty-two of them had received other types of stem cell transplantation before CBT. The cumulative incidences of neutrophil engraftment at day 50, grade II to IV acute graft-versus-host disease (GVHD), and chronic GVHD were 81.4%, 39.0%, and 19.5%, respectively. The incidence of nonrelapse mortality at 2 years was 39.0%, but it was only 6.2% in patients who underwent planned tandem autologous/reduced-intensity conditioning CBT (auto/RIC-CBT). Progression-free survival (PFS) and overall survival (OS) at 6 years were 13.0% and 15.2%, respectively. Less than a partial response before CBT and lack of prior transplantation were independent significant adverse factors for PFS, whereas the presence of prior transplantation and planned tandem transplantation were associated with better OS. OS at 6 years in patients who underwent auto/RIC-CBT was 45.9%. In addition, the development of chronic GVHD was associated with superior PFS. In conclusion, we demonstrated that cord blood is feasible as an alternative graft source for myeloma patients. Although CBT provided long-term survival for a fraction of patients, optimal use of this graft requires further clinical studies. [ABSTRACT FROM AUTHOR]

Allogeneic haematopoietic stem cell transplantation ( HSCT) is still considered to play an important role as a consolidation therapy for high-risk infants with acute lymphoblastic leukaemia ( ALL). Here, we retrospectively analysed outcomes of HSCT in infants with ALL based on nationwide registry data of the Japan Society for Haematopoietic Cell Transplantation. A total of 132 allogeneic HSCT for infant ALL with KMT2A ( MLL) gene rearrangements, which were performed in first complete remission ( CR1), were analysed. The 5-year overall survival rate after transplantation was 67·4 ± 4·5%). Although recent HSCT (after 2004) had a trend toward better survival, no statistical correlation was observed between outcomes and each factor, including age at diagnosis, initial leucocyte count, cytogenetics, donor types or conditioning of HSCT. Myeloablative conditioning with total body irradiation did not provide a better survival (60·7 ± 9·2%) over that with busulfan ( BU; 67·8 ± 5·7%). Two of the 28 patients treated with irradiation, but none of the 90 BU-treated patients, developed a secondary malignant neoplasm. In conclusion, allogeneic HSCT using BU was a valuable option for infant ALL with KMT2A rearrangements in CR1. [ABSTRACT FROM AUTHOR]

To evaluate haematopoietic stem cell transplantation ( HSCT) in children and adolescents, we reviewed the records of 47 patients who were ≤18 years, had relapsed or refractory anaplastic large cell lymphoma, and received HSCT between 1990 and 2010. At HSCT, complete remission ( CR) was less common in allogeneic HSCT recipients ( n = 24) than in autologous HSCT recipients ( n = 23) ( P = 0·01). The autologous and allogeneic HSCT groups differed in terms of 5-year event-free survival ( EFS) (38% vs. 50%, P = 0·63), cumulative incidence of progress or relapse (49% vs. 28%, P = 0·25), and treatment-related mortality (12% vs. 25%, P = 0·40). However, these differences were not significant. Patients with non- CR at autologous HSCT had a significantly lower EFS rate (14% vs. 48%, P = 0·03). Conversely, although those with non- CR at allogeneic HSCT had a lower EFS rate, this was not significant (44% vs. 63%, P = 0·26). Reduced-intensity conditioning regimens were used for three of the 16 allogeneic HSCTs received by patients with non- CR. These three patients achieved CR, surviving 32-65 months after HSCT. These results demonstrated that allogeneic HSCT might be a treatment option for patients who do not achieve CR through conventional chemotherapy. [ABSTRACT FROM AUTHOR]

Recent reports revealed that intravenous (iv) busulfan (BU) may not only reduce early nonrelapse mortality (NRM) but also improve overall survival (OS) probability in adults. Therefore, we retrospectively compared outcomes for 460 children with acute leukemia who underwent hematopoietic stem cell transplantation with either iv-BU (n = 198) or oral busulfan (oral-BU) (n = 262) myeloablative conditioning. OS at 3 years was 53.4% ± 3.7% with iv-BU and 55.1% ± 3.1% with oral-BU; the difference was not statistically significant (P = .77). OS at 3 years in 241 acute lymphoblastic leukemia and 219 acute myeloid leukemia patients was 56.4% ± 5.5% with iv-BU and 54.6% ± 4.1 with oral-BU (P = .51) and 51.0% ± 5.0% with iv-BU and 55.8% ± 4.8% with oral-BU (P = .83), respectively. Cumulative incidence of relapse at 3 years with iv-BU was similar to that with oral-BU (39.0% ± 3.6% and 36.4% ± 3.1%, respectively; P = .67). Cumulative incidence of NRM at 3 years was 16.6% ± 2.7% with iv-BU and 18.3% ± 2.5% with oral-BU (P = .51). Furthermore, multivariate analysis showed no significant survival advantage with iv-BU. In conclusion, iv-BU failed to show a significant survival advantage in children with acute leukemia. [ABSTRACT FROM AUTHOR]

Transient marrow expansion of normal B-cell precursors, termed hematogones, is occasionally observed after hematopoietic stem cell transplantation (HSCT). To understand the clinical significance of this phenomenon, we enumerated hematogones in 108 consecutive patients who received allogeneic HSCT for the treatment of hematologic malignancies, including acute myelogenous leukemia, advanced myelodysplastic syndromes, acute lymphoblastic leukemia, and non-Hodgkin lymphoma. Hematogone quantitation was performed at the time of complete donor engraftment (median day 25 and 32 in patients who received bone marrow and cord blood cell transplants, respectively). Hematogones were polyclonal B cells, and their frequencies correlated positively with blood B-cell numbers, and inversely with donors' but not recipients' age, suggesting that hematogones reflect cell-intrinsic B-cell potential of donor cells, Interestingly, patients developing hematogones that comprised > 5% of bone marrow mononuclear cells constituted a group with significantly prolonged overall survival and relapse-free survival, irrespective of their primary disease or donor cell source. In addition, patients with > 5% hematogones developed severe acute graft-versus-host diseases less frequently, which may contribute toward their improved survival. We therefore conclude that the amount of hematogones at the time of engraftment may be a useful tool in predicting the prognosis of patients treated with allogeneic HSCT. [ABSTRACT FROM AUTHOR]

Abstract: Hematopoietic stem cell transplantation (HSCT) has not been indicated for patients with mucopolysaccharidosis II (MPS II, Hunter syndrome), while it is indicated for mucopolysaccharidosis I (MPS I) patients <2years of age and an intelligence quotient (IQ) of ≥70. Even after the approval of enzyme replacement therapy for both of MPS I and II, HSCT is still indicated for patients with MPS I severe form (Hurler syndrome). To evaluate the efficacy and benefit of HSCT in MPS II patients, we carried out a nationwide retrospective study in Japan. Activities of daily living (ADL), IQ, brain magnetic resonance image (MRI) lesions, cardiac valvular regurgitation, and urinary glycosaminoglycan (GAG) were analyzed at baseline and at the most recent visit. We also performed a questionnaire analysis about ADL for an HSCT-treated cohort and an untreated cohort (natural history). Records of 21 patients were collected from eight hospitals. The follow-up period in the retrospective study was 9.6±3.5years. ADL was maintained around baseline levels. Cribriform changes and ventricular dilatation on brain MRI were improved in 9/17 and 4/17 patients, respectively. Stabilization of brain atrophy was shown in 11/17 patients. Cardiac valvular regurgitation was diminished in 20/63 valves. Urinary GAG concentration was remarkably lower in HSCT-treated patients than age-matched untreated patients. In the questionnaire analysis, speech deterioration was observed in 12/19 patients in the untreated cohort and 1/7 patient in HSCT-treated cohort. HSCT showed effectiveness towards brain or heart involvement, when performed before signs of brain atrophy or valvular regurgitation appear. We consider HSCT is worthwhile in early stages of the disease for patients with MPS II. [Copyright &y& Elsevier]

To compare the different stem cell sources used in salvage transplantation for graft failure (GF) after cord blood transplantation (CBT), we retrospectively analyzed data of 220 patients who developed GF after undergoing CBT between January 2001 and December 2007 and underwent a second hematopoietic stem cell transplantation (HSCT) within 3 months. The donor sources for salvage HSCT were cord blood (n = 180), peripheral blood stem cells (PBSCs; n = 24), and bone marrow (BM; n = 16). The cumulative incidence of neutrophil engraftment on day 30 after the second HSCT was 39% with CB, 71% with PBSCs, and 75% with BM. Multivariate analysis revealed that PBSC and BM grafts were associated with a significantly higher engraftment rate than CB (hazard ratio [HR], 7.77; P < .001 and HR, 2.81; P = .016, respectively). Although the incidence of grade II-IV acute graft-versus-host disease was significantly higher in the PBSC group than in the CB group (HR, 2.83; P = .011), the incidence of 1-year nonrelapse mortality was lower in the PBSC group than in the CB group (HR, 0.43; P = .019), and 1-year overall survival was superior in the PBSC group compared with the CB group (HR, 0.45; P = .036). Our results suggest that PBSC is the preferable source of stem cells in salvage HSCT for GF after CBT. [ABSTRACT FROM AUTHOR]

• Three-year OS and DFS rates of KMT2A -rearrageged pediatric AML was 52.1% and 46.7%. • Complete remission at HSCT was the most significant prognostic factor. • Supportive therapy and considering donor source might improve treatment outcomes. Pediatric acute myeloid leukemia (AML) with KMT2A rearrangement is detected in 15–20% of all pediatric AML patients and is associated with adverse outcomes even after allogeneic hematopoietic stem cell transplantation (HSCT). To investigate outcomes and prognostic factors, we investigated 90 pediatric AML patients with KMT2A rearrangement after allogeneic HSCT. We retrospectively analyzed Japanese registration data for patients who had received allogeneic HSCT between 1988 and 2011. Median age was 3 years (range, 0–15 years), and no gender difference was evident. Median observation period was 119 months. The 3-year overall survival (OS) rate of KMT2A -rearranged AML was 52.1% (95% confidence interval (CI), 42.4–64%, n = 90), and the 3-year disease-free survival (DFS) rate was 46.7% (95%CI, 36.8–58.2%). The 3-year DFS of KMT2A -rearranged AML was not significantly poorer than that of other AML (P = 0.09), and no significant difference was also seen in 3-year OS rate (P = 0.21). Multivariate analysis showed disease status (complete remission) at HSCT was associated with better outcomes. A significant difference in treatment-related mortality (TRM) was apparent between HSCT from a HLA full-matched related donor and that from a haploidentical donor (P = 0.001). HSCT is a curative option for pediatric AML with KMT2A rearrangement. Pretransplant status was the most significant prognostic indicator for relapse and survival. Enhancing supportive therapy to reduce TRM will further improve treatment outcomes of KMT2A -rearranged pediatric AML. [ABSTRACT FROM AUTHOR]

Adult T‐cell leukemia‐lymphoma (ATL) is a peripheral T‐cell lymphoma caused by human T‐cell lymphotropic virus type I. Previous retrospective studies suggested the presence of graft‐vs‐ATL (GV‐ATL) effects associated with acute graft‐vs‐host disease (GVHD), which suggests that intentional induction of acute GVHD to facilitate the efficacy of GV‐ATL effects might reduce the risk of relapse and contribute to improved survival after allogeneic hematopoietic stem cell transplantation. However, it is impractical to conduct a prospective study to assess the benefit of intentional induction of acute GVHD. In a simulation analysis using a Markov model, we assessed the impact on overall survival (OS) of changing the probability of overall acute GVHD and severe acute GVHD. When the probability of grade III‐IV acute GVHD changed from 0% to 100%, the expected 2‐year OS rate changed from 57.0% to 21.8% (48.2% of baseline at 2 years). When the probability of all grades of acute GVHD changed from 0% to 100%, the expected 2‐year OS rate changed from 48.2% to 49.5%. In conclusion, increasing the probability of overall acute GVHD was beneficial only when the proportion of grade III‐IV acute GVHD was lower than that in the original data. Based on the simulation results, preventive management of grade III‐IV acute GVHD is mandatory to achieve the clinical benefit associated with grade I‐II GVHD. [ABSTRACT FROM AUTHOR]