HLA-DPB1 mismatch induces a graft-versus-leukemia effect without severe acute GVHD after single-unit umbilical cord blood transplantation.

Although it is known that human leukocyte antigen (HLA)-DPB1 disparity has a strong impact on outcomes in unrelated hematopoietic transplantation with induction of acute graft-versus-host disease (GVHD) and a graft-versus-leukemia (GVL) effect, its role in unrelated umbilical cord blood transplantation (UR-CBT) has yet to be fully clarified. Our current study is being conducted to elucidate the impact of HLA-DPB1 mismatch, along with the effect of other HLA loci mismatches at the allele level. HLA six loci alleles were retrospectively typed in 1157 Japanese donors and patients with leukemia or myelodysplastic syndrome who underwent transplantation with a single unit of cord blood. HLA-DPB1 mismatch was associated with a significant reduction in leukemia relapse (hazard ratio 0.61, P<0.001), whereas the other HLA loci allele-level mismatches did not. No significant effect of HLA-DPB1 mismatch was observed in the risk of acute GVHD, engraftment or mortality. This HLA-DPB1 GVL effect without induction of severe acute GVHD or deterioration of survival rate has not been reported in unrelated bone marrow or peripheral blood stem cell transplantations, suggesting apparent advantages of UR-CBT. Accordingly, selection of an HLA-DPB1 mismatch cord blood might be the preferable choice for single-unit UR-CBT.

Impact of graft-versus-host disease on outcomes after unrelated cord blood transplantation.

The effect of graft-versus-host disease (GVHD) on transplant outcomes after unrelated cord blood transplantation (UCBT) has not been fully elucidated. We analyzed the impact of acute and chronic GVHD on outcomes in adult patients with acute leukemia or myelodysplastic syndrome who underwent their first UCBT (n=2558). The effect of GVHD on outcomes was analyzed after adjusting for other significant variables. The occurrence of GVHD was treated as a time-dependent covariate. The occurrence of grade 1-2 or 3-4 acute GVHD was significantly associated with a lower relapse rate. Grade 3-4 acute GVHD was associated with a higher risk of non-relapse and overall mortality than no acute GVHD, whereas grade 1-2 acute GVHD was associated with a lower risk of non-relapse and overall mortality than no acute GVHD. Limited or extensive chronic GVHD was significantly associated with a lower relapse rate. Limited chronic GVHD was associated with a lower overall and non-relapse mortality than no chronic GVHD. In conclusion, mild acute or chronic GVHD was associated not only with a low risk of relapse but also with a low risk of non-relapse mortality, and provides a survival benefit in UCBT.

Risk factors and prognosis of hepatic acute GvHD after allogeneic hematopoietic cell transplantation.

Hepatic acute GvHD (aGvHD) is associated with high mortality owing to poor response to immunosuppressive therapy. The pathogenesis of hepatic aGvHD differs from that of other lesions, and specific risk factors related to pre-transplant liver conditions should be determined. We conducted a cohort study by using a Japanese transplant registry database (N=8378). Of these subjects, 1.5% had hepatitis C virus Ab (HCV-Ab) and 9.4% had liver dysfunction (elevated transaminase or bilirubin levels) before hematopoietic cell transplantation (HCT). After HCT, the cumulative incidence of hepatic aGvHD was 6.7%. On multivariate analyses, HCV-Ab positivity (hazard ratio (HR), 1.93; P=0.02) and pre-transplant liver dysfunction (HR, 1.85; P<0.01), as well as advanced HCT risk, unrelated donors, HLA mismatch and cyclosporine as GvHD prophylaxis, were significant risk factors for hepatic aGvHD, whereas hepatitis B virus surface Ag was not. Hepatic aGvHD was a significant risk factor for low overall survival and high transplant-related mortality in all aGvHD grades (P<0.01). This study is the first to show the relationship between pre-transplant liver conditions and hepatic aGvHD. A prospective study is awaited to validate the results of this study and establish a new strategy especially for high-risk patients.

Sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: Incidence, risk factors and outcomes.

This retrospective study was conducted in Japan to determine the incidence, risk factors and outcomes of sinusoidal obstruction syndrome (SOS) after allogeneic hematopoietic stem cell transplantation (HSCT). Among 4290 patients undergoing allogeneic HSCT between 1999 and 2010, 462 were diagnosed with SOS according to the Seattle criteria (cumulative incidence, 10.8%). The cumulative incidence of SOS diagnosed by the modified Seattle criteria was 9.3%. Of 462 patients, 107 met the Baltimore criteria and 168 had severe SOS with renal and/or respiratory failure. The median onset for SOS was 12 days after HSCT (range, -2-30). Overall survival at day 100 was 32% for SOS and 15% for severe SOS. Multivariate analyses showed that significant independent risk factors for SOS were the number of HSCTs, age, performance status, hepatitis C virus-seropositivity, advanced disease status and myeloablative regimen. SOS was highly associated with overall mortality (hazard ratio, 2.09; P<0.001). Our retrospective survey showed that the cumulative incidence of SOS in Japan was 10.8%, similar to that previously reported in Western countries, and that the overall survival of patients who developed SOS was low. Furthermore, several risk factors were identified. Preventive and therapeutic strategies for high-risk SOS patients must be established to improve overall survival.

Pre-transplant diabetes mellitus is a risk factor for non-relapse mortality, especially infection-related mortality, after allogeneic hematopoietic SCT.

Diabetes mellitus (DM) is a factor in the hematopoietic cell transplantation-comorbidity index. However, the impact of pre-transplant DM on morbidity and cause-specific non-relapse mortality (NRM) remains unclear. We performed a retrospective study with registry data that included a total of 7626 patients who underwent their first allogeneic hematopoietic SCT (HSCT) between 2007 and 2010. The median age was 44 years (range 0-88). Compared with patients without pre-transplant DM (non-DM group, n=7248), patients with pre-transplant DM (DM group, n=378) were older and were more likely to have high-risk disease, a reduced-intensity conditioning regimen and GVHD prophylaxis using tacrolimus. Multivariate analyses showed that pre-transplant DM was associated with increased risks of NRM (hazard ratio (HR)1.46, 95% confidence interval (CI) 1.21-1.76, P<0.01) and infection-related NRM (HR 2.08, 95% CI 1.58-2.73, P<0.01). The presence of pre-transplant DM was associated with an increased risk of overall mortality in a multivariate analysis (HR 1.55, 95% CI 1.35-1.78, P<0.01). In conclusion, pre-transplant DM was a risk factor for NRM, particularly infection-related mortality, after allogeneic HSCT. To improve the clinical outcome in patients with DM, the benefits of strict infection control and appropriate glycemic control should be explored in future trials.

Decision analysis for donor selection in stem cell transplantation-HLA-8/8 allele-matched unrelated donor vs HLA-1 AG mismatched related donor.

Risk of relapse during the unrelated donor coordination period biases comparisons between allogeneic hematopoietic stem cell transplantation from an HLA 8 of 8 allele-matched unrelated donor (8/8 MUD) and that from a related donor with an HLA-1 antigen mismatch in the graft-versus-host (GVH) direction (RD/1AGMM-GVH). To reduce this bias, we performed a decision analysis focusing on acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in first complete remission (CR1). The primary outcome measure was 5-year survival probability with or without quality-of-life (QOL) adjustment. A baseline analysis showed that the decision to perform MUD transplantation was superior to that to perform RD/1AGMM-GVH transplantation for patients with AML or ALL. However, in the ALL cohort, the direction of superiority was reversed when the interval between CR1 and 8/8 MUD transplantation was >5.5 months (without QOL adjustment) or >6 months (after QOL adjustment) or when overall survival of RD/1AGMM-GVH transplantation improved by 1.3% without QOL adjustment and 2.1% after QOL adjustment. In conclusion, 8/8 MUD should be prioritized in transplantation for AML and ALL in CR1. However, the MUD coordination period and improvements in RD/1AGMM-GVH transplantation might change the donor selection priority in transplantation for ALL in CR1.

Impact of pretransplant body mass index on the clinical outcome after allogeneic hematopoietic SCT.

To elucidate the impact of pretransplant body mass index (BMI) on the clinical outcome, we performed a retrospective study with registry data including a total of 12 050 patients (age ⩾18 years) who received allogeneic hematopoietic SCT (HSCT) between 2000 and 2010. Patients were stratified as follows: BMI<18.5 kg/m(2), Underweight, n=1791; 18.5⩽BMI<25, Normal, n=8444; 25⩽BMI<30, Overweight, n=1591; BMI⩾30, Obese, n=224. The median age was 45 years (range, 18-77). A multivariate analysis showed that the risk of relapse was significantly higher in the underweight group and lower in the overweight and obese groups compared with the normal group (hazard ratio (HR), 1.16, 0.86, and 0.74, respectively). The risk of GVHD was significantly higher in the overweight group compared with the normal group. The risk of non-relapse mortality (NRM) was significantly higher in the overweight and obese group compared with the normal group (HR 1.19 and HR 1.43, respectively). The probability of OS was lower in the underweight group compared with the normal group (HR 1.10, P=0.018). In conclusion, pretransplant BMI affected the risk of relapse and NRM after allogeneic HSCT. Underweight was a risk factor for poor OS because of an increased risk of relapse. Obesity was a risk factor for NRM.

Continuing increased risk of oral/esophageal cancer after allogeneic hematopoietic stem cell transplantation in adults in association with chronic graft-versus-host disease.

BACKGROUND: The number of long-term survivors after hematopoietic stem cell transplantation (HSCT) showed steady increase in the past two decades. Second malignancies after HSCT are a devastating late complication. We analyzed the incidence of, risk compared with that in the general population, and risk factors for secondary solid cancers. PATIENTS AND METHODS: Patients were 17 545 adult recipients of a first allogeneic stem cell transplantation between 1990 and 2007 in Japan. Risks of developing secondary solid tumors were compared with general population by using standard incidence ratios (SIRs). RESULTS: Two-hundred sixty-nine secondary solid cancers were identified. The cumulative incidence was 0.7% [95% confidence interval (CI), 0.6%-0.9%] at 5 years and 1.7% (95% CI, 1.4%-1.9%) at 10 years after transplant. The risk was significantly higher than that in the general population (SIR=1.8, 95% CI, 1.5-2.0). Risk was higher for oral cancer (SIR=15.7, 95% CI, 12.1-20.1), esophageal cancer (SIR=8.5, 95% CI, 6.1-11.5), colon cancer (SIR=1.9, 95% CI, 1.2-2.7), skin cancer (SIR=7.2, 95% CI, 3.9-12.4), and brain/nervous system cancer (SIR=4.1, 95% CI, 1.6-8.4). The risk of developing oral, esophageal, or skin cancer was higher at all times after 1-year post-transplant. Extensive-type chronic graft-versus-host disease (GVHD) was a significant risk factor for the development of all solid tumors (RR=1.8, P<0.001), as well as for oral (RR=2.9, P<0.001) and esophageal (RR=5.3, P<0.001) cancers. Limited-type chronic GVHD was an independent risk factor for skin cancers (RR=5.8, P=0.016). CONCLUSION: Recipients of allogeneic HSCT had a significantly higher ∼2-fold risk of developing secondary solid cancers than the general population. Lifelong screening for high-risk organ sites, especially oral or esophageal cancers, is important for recipients with active, or a history of, chronic GVHD.

Allogeneic transplantation for primary myelofibrosis with BM, peripheral blood or umbilical cord blood: an analysis of the JSHCT.

To determine whether a difference in donor source affects the outcome of transplantation for patients with primary myelofibrosis (PMF), a retrospective study was conducted using the national registry data on patients who received first allogeneic hematopoietic cell transplantation (HCT) with related BM (n=19), related PBSCs (n=25), unrelated BM (n=28) or unrelated umbilical cord blood (UCB; n=11). The 5-year OS rates after related BM, related PBSC and unrelated BM transplantation were 63%, 43% and 41%, respectively, and the 2-year OS rate after UCB transplantation was 36%. On multivariate analysis, the donor source was not a significant factor for predicting the OS rate. Instead, performance status (PS) ≥2 (vs PS 0-1) predicted a lower OS (P=0.044), and RBC transfusion ≥20 times before transplantation (vs transfusion ≤9 times) showed a trend toward a lower OS (P=0.053). No advantage of nonmyeloablative preconditioning regimens in terms of decreasing nonrelapse mortality or increasing OS was found. Allogeneic HCT, and even unrelated BM and UCB transplantation, provides a curative treatment for PMF patients.

Risk factors and organ involvement of chronic GVHD in Japan.

Few studies have evaluated the risk factors for chronic GVHD and organ involvement associated with different graft types, including unrelated cord blood (U-CB). We retrospectively studied 4818 adult patients who received their first allogeneic transplantation and survived for at least 100 days. The incidence of chronic GVHD at 2 years was 37%. The following factors were associated with the development of chronic GVHD: female donor/male recipient, CMV-Ab seropositivity, matched related peripheral blood grafts vs matched related BM grafts, no in vivo T-cell depletion and the occurrence of grade II-IV acute GVHD. Among these factors, the association with acute GVHD occurrence was consistently significant across donor subtypes. The use of U-CB was not associated with chronic GVHD, but was associated with a low incidence of extensive chronic GVHD. Chronic GVHD patients who had received U-CB transplants showed less frequent involvement of the oral cavity (28% vs 55%), eye (12% vs 26%), liver (20% vs 44%), lung (11% vs 25%) and joint (0% vs 6%) than those with matched related BM grafts. In conclusion, we found that U-CB transplants were associated with a low incidence of extensive chronic GVHD and less frequent involvement of the oral cavity, eye, liver, lung and joints.

PBSC collection from family donors in Japan: a prospective survey.

Severe adverse events (SAE) and late hematological malignancies have been reported after PBSC donation. No prospective data on incidence and risk factors have been available for family donors so far. The Japan Society for Hematopoietic Cell Transplantation (JSHCT) introduced therefore in 2000 a mandatory registration system. It defined standards for donor eligibility and asked harvest centers to report any SAE immediately. All donors were examined at day 30 and were to be contacted once each year for a period of 5 years. Acute SAEs within day 30 were reported from 47/3264 donations (1.44%) with 14 events considered as unexpected and severe (0.58%). No donor died within 30 days. Late SAEs were reported from 39/1708 donors (2.3%). The incidence of acute SAEs was significantly higher among donors not matching the JSHCT standards (P=0.0023). Late hematological malignancies in PBSC donors were not different compared with a retrospective cohort of BM donors (N:1/1708 vs N:2/5921; P=0.53). In conclusion, acute and late SAEs do occur in PBSC donors at relatively low frequency but risk factors can be defined.

Impact of being overweight on outcomes of hematopoietic SCT: a meta-analysis.

The impact of being overweight on outcome after hematopoietic SCT (HSCT) is controversial. We performed meta-analyses to evaluate the impact of being overweight on acute graft-versus-host disease (aGVHD) risk and survival. Original data were obtained from MEDLINE, and studies that evaluated being overweight before transplantation in recipients as a risk factor for aGVHD or a prognostic factor for overall survival (OS) were extracted. Study-specific relative risks on the log scale comparing overweight with non-overweight patients were used to obtain a pooled RR with 95% confidence interval (CI). We identified 8 studies of aGVHD and 21 of OS. In allogeneic HSCT, the meta-analysis determined statistically significant associations of overweight recipients with aGVHD risk and OS. Meta-analysis of the 8 studies of aGVHD indicated that the RR for overweight to non-overweight patients was 1.186 (95% CI: 1.072-1.312). Regarding OS, meta-analysis of 11 allogeneic HSCT studies indicated that the RR for overweight to non-overweight patients was 1.163 (1.009-1.340). Our results indicate that being overweight before transplantation in recipients is associated with a high aGVHD rate and worse survival after allogeneic HSCT. Potential heterogeneity especially in adult/pediatric patients limits the interpretability of our finding. Further, well-designed large cohort studies are warranted.

Effects of KIR ligand incompatibility on clinical outcomes of umbilical cord blood transplantation without ATG for acute leukemia in complete remission.

To clarify the effect of killer cell immunoglobulin-like receptor (KIR) ligand incompatibility on outcomes of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients in complete remission after single cord blood transplantation (CBT), we assessed the outcomes of CBT registered in the Japan Society for Hematopoietic Cell Transplantation (JSHCT) database. A total of 643 acute leukemia (357 AML and 286 ALL) patient and donor pairs were categorized according to their KIR ligand incompatibility by determining whether or not they expressed HLA-C, Bw4 or A3/A11 by DNA typing. A total of 128 patient-donor pairs were KIR ligand-incompatible in the graft-versus-host (GVH) direction and 139 patient-donor pairs were incompatible in the host-versus-graft (HVG) direction. Univariate and multivariate analyses showed no significant differences between the KIR ligand-incompatible and compatible groups in the GVH direction for both AML and ALL patients of overall survival, disease-free survival, relapse incidence, non-relapse mortality and acute GVH disease. However, KIR incompatibility in the HVG direction ameliorated engraftment in ALL patients (hazard ratio 0.66, 95% confidence interval 0.47-0.91, P=0.013). Therefore, there were no effects of KIR ligand incompatibility in the GVH direction on single CBT outcomes for acute leukemia patients without anti-thymocyte globulin use. However, it is necessary to pay attention to KIR incompatibility in the HVG direction for engraftment.

Reduced-intensity allogeneic stem cell transplantation for patients aged 50 years or older with B-cell ALL in remission: a retrospective study by the Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation.

We retrospectively assessed the outcome and pretransplantation predictors of the outcome in 118 patients aged ≥ 50 years who received fludarabine-containing reduced-intensity allo-SCT (RIST) for B-cell ALL in the first or second CR. Eighty patients received transplants from unrelated donors. Seventy-eight patients were positive for the Ph chromosome. The median follow-up period was 18 months and the 2-year OS rate was 56%. The 2-year cumulative incidence of relapse and non-relapse mortality was 28% and 26%, respectively. The incidence of grades II-IV and III-IV acute GVHD was 46% and 24%, respectively. After 2 years, the incidence of chronic GVHD was 37%. Multivariate analysis of pretransplant factors showed that a higher white blood cell count (≥ 30 × 10(9)/L) at diagnosis (hazard ratio (HR)=2.19, P=0.007) and second CR (HR=2.02, P=0.036) were significantly associated with worse OS, whereas second CR (HR=3.83, P<0.001) and related donor (HR=2.34, P=0.039) were associated with a higher incidence of relapse. Fludarabine-containing RIST may be a promising strategy for older patients with B-cell ALL in their first remission.

Pre-transplant risk factors for cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia after hematopoietic cell transplantation.

Cryptogenic organizing pneumonia (COP), previously known as bronchiolitis obliterans organizing pneumonia (BOOP), is a significant complication after allogeneic hematopoietic SCT (HCT). However, the pathogenesis of this complication has not yet been elucidated. Therefore, we identified the pre-transplant risk factors for the development of COP/BOOP using the Japan transplant registry database between 2005 and 2009. Among 9550 eligible recipients, 193 experienced COP/BOOP (2%). HLA disparity (odds ratio (OR) 1.51, P=0.05), female-to-male HCT (OR 1.53, P=0.023), and PBSC transplant (OR 1.84, P=0.0076) were significantly associated with an increased risk of COP/BOOP. On the other hand, BU-based myeloablative conditioning (OR 0.52, P=0.033), or fludarabine-based reduced-intensity conditioning (OR 0.50, P=0.0011) in comparison with a TBI-based regimen and in vivo T-cell depletion (OR 0.46, P=0.055) were associated with a lower risk. Of the 193 patients with COP/BOOP, 77 died, including non-relapse death in 46 (59%). Pulmonary failure and fatal infection accounted for 41% (n=19) and 26% (n=12) of the non-relapse death. Allogeneic immunity and conditioning toxicity could be associated with COP/BOOP. Prospective studies are required to elucidate the true risk factors for COP/BOOP and to develop a prophylactic approach.

Reduced-intensity vs myeloablative conditioning allogeneic hematopoietic SCT for patients aged over 45 years with ALL in remission: a study from the Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT).

In this study, outcomes for 575 adult ALL patients aged ≥45 years who underwent first allo-SCT in CR were analyzed according to the type of conditioning regimen (myeloablative conditioning (MAC) for 369 patients vs reduced-intensity conditioning (RIC) for 206 patients). Patients in the RIC group were older (median age, 58 vs 51 years, P<0.0001). There were no statistically significant differences in 3-year OS, disease-free survival (DFS) and non-relapse mortality (NRM): 51% vs 53%, 47% vs 39% and 38% vs 36%, respectively. Multivariate analysis showed that CR2 and HLA mismatching were associated with poor OS (P=0.002 and P=0.019, respectively). HLA mismatching was associated with lower rate of relapse (P=0.016), but was associated with higher rate of NRM (P=0.001). RIC was associated with good OS and DFS in patients who received HLA-mismatch transplantation and were aged ≥55 years compared with MAC by multivariate analysis for each event with interaction (hazard ratio (HR) and 95% confidence interval 0.35 and 0.15-0.81, P=0.014 for OS and 0.36 and 0.16-0.81, P=0.013 for DFS). Therefore, patients ≥55 years of age with HLA-mismatch transplantation should be candidates for RIC rather than MAC.

Recent decrease in non-relapse mortality due to GVHD and infection after allogeneic hematopoietic cell transplantation in non-remission acute leukemia.

Although recent improvements have been indicated in the outcome after allogeneic hematopoietic cell transplantation (allo-HCT), little information is available on how changes in transplant modalities have affected the outcomes after allo-HCT in non-remission, based on patient age, donor source and disease type. We compared the incidence and causes of non-relapse mortality (NRM) after allo-HCT in non-remission among three consecutive four-year periods using a nationwide transplant outcome registry database. A total of 3308 patients with acute leukemia in non-remission were analyzed. The risk of NRM decreased over the three periods, and the hazard ratios (HRs) in 2001-2004 and 2005-2008 compared with 1997-2000 were 0.86 (95% CI, 0.70-1.06; P=0.16) and 0.65 (95% CI, 0.53-0.80; P<0.01), respectively. A significant decrease in the HR for overall mortality was also observed in 2005-2008 (HR 0.85; 95% CI, 0.75-0.97; P=0.02). We found that a decrease in the incidences of death due to GVHD and infection contributed to the reduction in NRM, to which high-resolution donor-recipient HLA matching and other improvements may have contributed. As none of the subgroups showed improved survival without a reduction in NRM, the effective prevention of transplant-related complications appears to be necessary for improving outcomes after allo-HCT in non-remission.

Impact of a donor source on adult Philadelphia chromosome-negative acute lymphoblastic leukemia: a retrospective analysis from the Adult Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation.

BACKGROUND: We aimed to clarify the impact of the donor source of allogeneic stem cell transplantation (allo-SCT) on Philadelphia chromosome-negative acute lymphoblastic leukemia [Ph(-) ALL] with focus on cord blood (CB). PATIENTS AND METHODS: We retrospectively analyzed data of 1726 patients who underwent myeloablative allo-SCT for adult Ph(-) ALL. The sources of the allo-SCT were related donors (RD; N = 684), unrelated donors (URD; N = 809), and CB (N = 233). RESULTS: Overall survival (OS) in patients after CB allo-SCT in first complete remission (CR1) was comparable with that after RD or URD allo-SCT (RD: 65%, URD: 64% and CB: 57% at 4 years, P = 0.11). CB was not a significant risk factor for relapse or non-relapse mortality as well as for OS in multivariate analyses. Similarly, the donor source was not a significant risk factor for OS in subsequent CR or non-CR (RD: 47%, URD: 39% and CB: 48% in subsequent CR, P = 0.33; RD: 15%, URD: 21% and CB: 18% in non-CR, P = 0.20 at 4 years). CONCLUSION: Allo-SCT using CB led to OS similar to those of RD or URD in any disease status. To avoid missing the appropriate timing, CB is a favorable alternative source for adult Ph(-) ALL patients without a suitable RD or URD.

The role of HLA-matched unrelated transplantation in adult patients with Ph chromosome-negative ALL in first remission. A decision analysis.

The efficacy of unrelated transplantation for patients with ALL who lack an HLA-matched sibling remains unclear. We performed a decision analysis to determine the efficacy of myeloablative transplantation from a genetically HLA-A, -B, -DRB1 allele-matched unrelated donor for patients with Ph chromosome-negative ALL aged 21-54 years. The transition probabilities were estimated from the Japan Adult Leukemia Study Group studies (ALL93; n=80, ALL97; n=82), and the Japan Marrow Donor Program database (transplantation in first CR (CR1): n=177). The primary outcome measure was the 10-year survival probability with or without quality of life (QOL) adjustment. Subgroup analyses were performed according to risk stratification based on the WBC count and cytogenetics, and according to age stratification. In all patients, unrelated transplantation in CR1 was shown to be superior in analyses both with and without QOL adjustment (40.8 vs 28.4% and 43.9 vs 29.0%, respectively). A similar tendency was observed in all subgroups. The decision model was sensitive to the probability of leukemia-free survival following chemotherapy and the probability of survival after transplantation in standard-risk and higher-aged patients. Unrelated transplantation in CR1 improves the long-term survival probability in patients who lack an HLA-matched sibling. However, recent improvements in treatment strategies may change this result.