Hemophagocytic lymphohistiocytosis is a sign of poor outcome in pediatric Epstein-Barr virus-associated post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation.

EBV-related PTLD developing after HSCT is a potentially life-threatening disease. HLH is uncommon after allogeneic HSCT. Data on outcome of patients with PTLD and concomitant HLH after allogeneic HSCT are limited. In this retrospective study, we collected demographic, clinical, laboratory, and outcome data for 408 patients who underwent allogeneic HSCT from 2006 to 2015. Graft source included CB (n = 135; 33.1%), PBSCs (n = 34; 8.3%), and BM (n = 239; 58.6%). Eight out of 408 patients (2%) developed EBV-PTLD with a median age at HSCT of 5.9 years (range: 2.3-17.3). All eight patients received ATG as part of the conditioning regimen. Graft source was PBSC in three patients (37.5%), BM in four patients (50%), and CB in one patient (12.5%). Donors were matched unrelated in five patients (62.5%) and matched sibling in three patients (37.5%). Seven out of eight patients developed EBV-PTLD within the first 100-day post-HSCT. Lymph node biopsy revealed early lesions in three patients, polymorphic in three patients, and monomorphic PTLD in two patients. Three patients (37.5%) died within 1 month of EBV-PTLD diagnosis. All deceased patients developed HLH manifestations with two of them meeting HLH diagnostic criteria and one having an incomplete workup. PTLD after allogeneic HSCT with manifestations of HLH is associated with high mortality. Early identification and treatment of EBV-PTLD seems imperative to control the disease, especially if signs of HLH are evolving.

Collection of hematopoietic stem cells and immune effector cells in small children.

Apheresis procedures are standard of care for a wide range of indications in children, collection of hematopoietic stem cells being the most frequent one. With increasing numbers of hematopoietic stem cell transplants, advances in graft manipulation techniques and the development of innovative therapies using immune effector cells and gene therapy, apheresis within the pediatric population is growing in demand. While young children have higher circulating white blood cell counts and robustly mobilize hematopoietic stem cells, apheresis machines were designed for use within the adult population and apheresis procedures in children, particularly small children, can be more challenging as vascular access, collection techniques and impact of extracorporeal volumes increase the rate of adverse events. In this article we review topics of particular relevance to hematopoietic stem cell and immune effector cell collections in small children.

A Multicenter Retrospective Analysis Stressing the Importance of Long-Term Follow-Up after Hematopoietic Cell Transplantation for ß-Thalassemia.

Allogeneic hematopoietic cell transplantation (HCT) is curative in patients with ß-thalassemia major. However, most reports on HCT outcomes lack long-term follow-up data with the exception of single-center reports. An international multicenter retrospective data collection and analysis was conducted in 176 ß-thalassemia patients who were 1 year or beyond after first HCT to evaluate follow-up methods and outcomes at 7 centers. Median age at HCT was 5.5 years (range, .6 to 18.5), and median follow-up was 7 years (range, 1 to 20). HCT was predominantly from HLA-matched related donors (91%) with bone marrow as stem cell source (91%) and myeloablative conditioning regimens (88%). Late mortality or persistent chronic graft-versus-host disease (GVHD) was rare (<2%). Graft rejection was reported in 23% (24% of these occurred beyond 1 year) post-HCT. Of 119 patients with donor chimerism results available for ≥4 years post-HCT, 50% had >95%, 22% had 50% to 95%, 7% had 20% to 50% and 25 (21%) had <20% donor chimerism. Organ dysfunction was identified in 10% pre-HCT and in 20% post-HCT even without complete clinical details on all patients. Hypogonadism and elevated creatinine for age were most commonly reported and significantly higher in recipients ≥ 7 years at the time of HCT (P = .007) and in those with pre-existing morbidity before HCT (P = .02). Outcomes were unaffected by pre-HCT ferritin or GVHD. Mean z scores for height and weight were low at baseline and remained low post-HCT (79%), confirming that growth impairment from disease lacked recovery post-HCT during this follow-up period. HCT for ß-thalassemia has a high rate of cure and low mortality, especially in the young and from HLA-matched related donors. Half of the number of recipients live with mixed chimerism that requires continued follow-up because of a risk of late graft rejection (14%). Organ function after HCT when <7 years of age was generally preserved. Hypogonadism, renal dysfunction, and growth impairment that failed to correct were late complications identified most frequently in older transplant recipients. Systematic follow-up of individual organs such as lung and heart were inadequate but important. These data support the development of simple measures of uniformly tracking long-term HCT outcomes and organ functions in children and adolescents who undergo HCT for thalassemia, allowing for systematic identification and implementation of standardized surveillance strategies and interventions.

Relative defects in mucosal immunity predict acute graft-versus-host disease.

Impairment of gut mucosal immunity by the transplant process could facilitate translocation of commensal bacteria and thereby augment the graft-versus-host response. To begin to assess the influence of gut mucosal immunity on the development of acute graft-versus-host disease (GVHD), we conducted a prospective study in 24 pediatric allogeneic hematopoietic cell transplant recipients, assessing 4 fecal markers of mucosal immunity: calprotectin, soluble CD8 (sCD8), soluble intracellular adhesion molecule 1, and ß-defensin-2. Stool samples were collected prospectively on transplant days 0, +5, +10, and +15 and analyzed by ELISA. Lower levels on day +5 (calprotectin and ß-defensin-2) and day +10 (calprotectin, ß-defensin-2, and sCD8) were associated with subsequent acute GVHD. The most striking difference was with calprotectin on day +10. Patients with levels below 424 mg/kg had an incidence of 77.8%, whereas those with levels above this threshold had a cumulative incidence of 0% (P = .002). Relative defects in gut mucosal immunity may be important in the pathogenesis of acute GVHD.

Pediatric hematology/oncology healthcare professional emotional health during COVID-19.

OBJECTIVES: Little is known about the impact of coronavirus disease 2019 (COVID-19) on healthcare professional emotional health in pediatric hematology/oncology. Primary objective was to describe anxiety, depression, positive affect, and perceived stress among pediatric hematology/oncology healthcare professionals following a COVID-19 outbreak. Secondary objectives were to compare these outcomes based on contact with a positive person, and to identify risk factors for worse outcomes. MATERIALS AND METHODS: We included 272 healthcare professionals working with pediatric hematology/oncology patients. We determined whether respondents had direct or indirect contact with a COVID-19-positive individual and then measured outcomes using the Patient-Reported Outcomes Measurement Information System (PROMIS) depression, anxiety, and positive affect measures, and the Perceived Stress Scale. RESULTS: Among eligible respondents, 205 agreed to participate (response rate 75%). Sixty-nine (33.7%) had contact with a COVID-19-positive person. PROMIS anxiety, depression, and positive affect scores were similar to the general United States population. Those who had contact with a COVID-19-positive individual did not have significantly different outcomes. In multiple regression, non-physicians had significantly increased anxiety (nurses: p = 0.013), depression (nurses: p = 0.002, pharmacists: p = 0.038, and other profession: p = 0.021), and perceived stress (nurses: p = 0.002 and other profession: p = 0.011) when compared to physicians. CONCLUSIONS: Pediatric hematology/oncology healthcare professionals had similar levels of anxiety, depression, and positive affect as the general population. Contact with a COVID-19-positive individual was not significantly associated with outcomes. Non-physician healthcare professionals had more anxiety, depression, and perceived stress when compared to physicians. These findings may help to develop programs to support healthcare professional resilience.

Long term disease-free survival in acute leukemia patients recovering with increased gammadelta T cells after partially mismatched related donor bone marrow transplantation.

Allogeneic stem cell transplantation (ASCT) has improved leukemia-free survival (LFS) in many but not all patients with acute leukemia. This is an eight-year follow-up to our previous study showing a survival advantage to patients with an increased gammadelta T cells following ASCT. gammadelta T cell levels were collected prospectively in 153 patients (acute lymphoblastic leukemia (ALL) n = 77; acute myelogenous leukemia (AML) n = 76) undergoing partially mismatched related donor ASCT. Median age was 22 years (1-59), and 62% of the patients were in relapse at transplant. Patient-donor human leukocyte antigen (HLA) disparity of three antigens was 37% in the graft-versus-host disease (GvHD) and 29% in the rejection directions. All patients received a partially T cell-depleted graft using T10B9 (n = 46) or OKT3 (n = 107). Five years LFS and overall survival (OS) of patients with increased gammadelta compared to those with normal/decreased numbers were 54.4 vs 19.1%; P < 0.0003, and 70.8 vs 19.6% P < 0.0001, respectively, with no difference in GvHD (P = 0.96). In a Cox multivariate analysis, normal/decreased gammadelta (hazard ratio (HR) 4.26, P = 0.0002) and sex mismatch (HR 1.45 P=0.049) were associated with inferior LFS. In conclusion, gammadelta T cells may facilitate a graft-versus-leukemia (GvL) effect, without causing GvHD. Further evaluations of this effect may lead to specific immunotherapy for patients with refractory leukemia.

The safety of autologous and metabolically fit bone marrow mesenchymal stromal cells in medically refractory Crohn's disease - a phase 1 trial with three doses.

BACKGROUND: Mesenchymal stromal cells ability to reset immune functionalities may be useful in Crohn's disease. AIM: To perform a first-in-human phase 1 safety clinical trial of metabolically fit autologous bone marrow-derived mesenchymal stromal cells in 12 subjects with Crohn's disease utilising three doses. METHODS: Autologous mesenchymal stromal cells were derived from marrow aspirate and propagated for 2-3 weeks with fibrinogen depleted human platelet lysate and subsequently administered to subjects without interval cryobanking. Twelve subjects received a single mesenchymal stromal cell intravenous infusion of 2, 5 or 10 million cells/kg BW(n = 4/group). Infused mesenchymal stromal cells were analysed for cell surface marker expression, IDO(indoleamine 2,3-dioxygenase) upregulation by IFNγ stimulation, and inhibition of third party peripheral blood mononuclear cell proliferation in vitro. The primary end point measured was safety and tolerability; clinical response was assessed as a secondary endpoint. RESULTS: All patients tolerated the mesenchymal stromal cell infusion well and no dose limiting toxicity was seen. Seven patients had serious adverse events of which five were hospitalisations for Crohn's disease flare. Two of these serious adverse events were possibly related to the mesenchymal stromal cells infusion. Five subjects showed clinical response 2 weeks after the infusion. Mesenchymal stromal cell phenotype, cytokine responsiveness, and peripheral blood mononuclear cell proliferation blockade were not different among the patients. CONCLUSION: Single infusion of fresh autologous bone marrow mesenchymal stromal cells propagated ex vivo using human platelet lysate-supplemented media was safe and feasible at intravenous doses of up to 10 million cells/kg BW in patients with Crohn's disease.

Partially mismatched related-donor bone marrow transplantation for pediatric patients with acute leukemia: younger donors and absence of peripheral blasts improve outcome.

PURPOSE: To extend access to bone marrow transplantation (BMT), we used partially mismatched related donors (PMRD) for pediatric patients with acute leukemia. In this report we sought to determine pretransplantation factors that might predict outcome. PATIENTS AND METHODS: Of 67 such patients, 43 had acute lymphocytic leukemia and 24 had acute myelogenous leukemia. At the time of transplantation, 41 patients were in relapse. Donors included 40 parents, 24 siblings, and three cousins. HLA disparity of two to three major antigens was detected in two thirds of the donor-recipient pairs. Conditioning therapy, including total-body irradiation and chemotherapy followed by graft-versus-host disease (GvHD) prophylaxis with partial T-cell depletion of the graft using T10B9 or OKT3, was combined with posttransplantation immunosuppression. RESULTS: Estimated probability (EP) of engraftment was 0.96 and was not affected by donor-antigen mismatch (AgMM; P =.732). EP of grades 2 to 4 acute GvHD was 0.24 and was not affected by recipient AgMM (P =.796). EP of disease-free survival was 0.26 at 3 years but improved to 0.45 when donors were younger than 30 years (P<.001). EP of relapse at 3 years was 0.41 and reduced with younger donors' age. For patients who were in relapse at the time of transplantation, absence of blasts was associated with a lower relapse rate (0.46 v. 0.84; P =. 083), similar to that of patients in remission. CONCLUSION: PMRD-BMT in pediatric leukemia resulted in high engraftment and low GvHD rates. To improve outcomes, younger donors should be sought, and clinicians should attempt to reduce peripheral blasts in patients who are in relapse.

A nation-wide population-based study of inguinal hernia repair incidence and age-stratified recurrence in an Asian population.

PURPOSE: It has been estimated in the UK that 27 % of men and 3 % of women will undergo an inguinal hernia repair (IHR) during their lifetimes. However, no epidemiologic study investigating IHR has been performed to date in an Asian population. The present study explored the incidence and recurrence of IHR in an Asian population using a nation-wide population-based dataset in Taiwan. METHODS: Based on the National Health Insurance Database, we identified 5806 patients who underwent an IHR between 2000 and 2010 and followed them until they had a recurrence, died during hospitalization, left the program, or the study ended. We calculated the age-stratified recurrence rates and used Cox proportional hazards to explore the influence of demographic and clinical factors on recurrence. We also plotted IHR occurrence over the study period. RESULTS: Among the 5806 sampled subjects who had an IHR, 565 (9.73 %) had an IHR recurrence yielding an overall incidence of 18.23 per 1000 person-years. The hazard ratios for recurrence increased with age, and were greater among men and blue collar workers. The incidence of IHR decreased from 168.21 to 92.10 per 100,000 person-years over the study period. Surgical complication rates ranged between 0.16 and 2.57 %. CONCLUSIONS: On account of the increased risk of recurrence with age, young hernia patients may not want to delay surgery. This study detected a decreasing trend in initial IHR rates, confirming similar trends reported in Western countries. However, the incidence of initial IHR is lower in Taiwan than it is in the West.

Should we be performing more combined hematopoietic stem cell plus solid organ transplants?

Both bone marrow and solid organ transplants (SOTs) can be life saving for a wide variety of diseases. We reviewed the literature and summarized the experiences of dual transplants. In total, 37 patients received a SOT for organ failure after a previous hematopoietic stem cell transplant. In all, 12 subjects received SOTs followed by a bone marrow transplant, while three patients received simultaneous SOTs and bone marrow transplants. Of these 52 patients, 37 were alive at the time of the original report at follow-up times ranging from 3 months to 8 years. A special registry for data collection may prove helpful for obtaining long-term follow-up data and providing outcome information that may improve future patient survival.

Non-myeloablative allogeneic transplantation ('microallograft') for refractory myeloma after two preceding autografts: feasibility and efficacy in a patient with active aspergillosis.

A 59-year-old man with a 4-year history of light chain myeloma relapsing after two preceding autografts and salvage therapy with thalidomide underwent a peripheral blood stem cell (PBSC) transplant from his HLA-identical sister after conditioning with 100 mg/m2 melphalan. Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine. Despite pulmonary infiltrates and sinusitis at the time of the allograft, it was decided to proceed with the transplant because the myeloma was refractory and rapidly progressive. Sputum cultures obtained 2 days before the allograft grew Aspergillus fumigatus 2 days post transplant. A fumigatus grew repeatedly on specimens obtained post transplant. Prompt hematologic recovery was seen with full donor-type chimerism. The fungal infection subsided gradually on a combination of amphotericin B lipid complex and itraconazole. A second aliquot of donor PBSC was infused electively on day +42 to induce graft-versus-myeloma. Complete remission of the myeloma was achieved by 75 days post transplant. No acute GVHD was seen. No chronic GVHD was seen at 16 weeks when he received the third PBSC infusion. He is currently alive and well in remission 9 months post transplant. This case demonstrates the safety and potential usefulness of allogeneic PBSC transplantation with reduced-intensity conditioning in patients with markedly compromised performance status.

Allogeneic bone marrow transplantation from partially mismatched related donors as therapy for primary induction failure acute myeloid leukemia.

The outcome of acute myeloid leukemia patients with primary refractoriness to conventional chemotherapy is extremely poor. Allogeneic bone marrow transplants with matched sibling or matched unrelated donors provide 10-20% disease-free survival in this setting. We analyzed our transplant experience using readily available partially mismatched related donor (PMRD) in patients with primary induction failure (PIF) AML. Between March 1994 and December 1998, 13 patients with PIF AML were transplanted from 0-3 HLA antigen mismatched donors. All 12 evaluable patients engrafted at a median of day +16. Ten (77%) patients survived at least 100 days after transplant. Acute GVHD (grade II) was observed in one of 12 patients. Chronic GVHD was seen in one of 10 patients surviving beyond day 100. The major cause of failure was relapse of disease in six occurring 3-12 months after PMRD BMT. Three patients are alive without disease 14, 36 and 45 months post BMT with Karnofsky scores of 100%. The actuarial 3-year probabilities of relapse and disease-free survival were 0.54 and 0.19, respectively. We concluded that a PMRD graft is a viable option, comparable to the use of matched related or unrelated donors, in patients with PIF AML in whom time is of the essence.

Transplantation of unrelated placental blood cells in children with high-risk sickle cell disease.

The lack of healthy HLA-identical sibs limits the use of allogeneic hematopoietic cell transplantation in children with high-risk sickle cell disease (SCD). We evaluated unrelated placental blood cell transplantation (UPBCT) after a preparative regimen of busulfan, cyclophosphamide and antithymocyte globulin in three children with SCD who had cerebrovascular accidents (CVAs) and did not have HLA-matched sib donors. The placental blood cell units were matched with the recipients at four of six HLA-A, HLA-B and HLA-DRB1 antigens. Neutrophil levels above 0.5 x 10(9)/l occurred at 23, 38 and 42 days after UPBCT, and platelet levels above 50 x 10(9)/l without transfusions occurred at 62, 81 and 121 days after UPBCT. All patients developed acute graft-versus-host disease (GVHD; two grade II, one grade III), and one developed extensive chronic GVHD. One patient had graft failure and autologous hematopoietic recovery. Two patients have complete donor hematopoietic chimerism without detectable hemoglobin S or symptoms of SCD at 40 and 61 months, respectively, after UPBCT. These observations demonstrate the feasibility of UPBCT in children with SCD. Further studies of UPBCT for SCD are needed but, because of risks of procedure-related morbidity and graft rejection, should be restricted to pediatric patients with high-risk manifestations of SCD.

Epstein-Barr virus-associated B cell lymphoproliferative disorder following mismatched related T cell-depleted bone marrow transplantation.

Epstein-Barr virus (EBV) is closely associated with the progressive and often fatal lymphoproliferative disorders (LPD) in post bone marrow transplantation (BMT) and immunocompromised hosts. The incidence increases significantly when alternative donors or manipulation of marrow graft are used. A total of 318 consecutive BMT from partially mismatched related family donors (PMRD) were performed between February 1993 and June 1998. Known risk factors for the development of EBV-LPD were analyzed which included HLA mismatches, T cell depletion, antithymocyte globulin (ATG), and graft-versus-host disease (GVHD). Eighteen patients (5.7%) developed EBV-LPD at a median of 137 days post BMT (range 48-617). The estimated probability of developing EBV-LPD was 0.13 (95% CI 0.07-0.19) at 5 years. The incidence of grade II to IV GVHD was 19.2%, which translated into an increased trend of EBV-LPD. No correlation with other risk factors was observed. Treatment consisted of supportive antiviral agents, tapering of immunosuppressive regimens, donor leukocyte infusions and radiation. Three patients are alive and disease-free at a median follow-up of 69 months (range 36-71). We observed a lower than expected incidence of EBV-LPD despite existing multiple high-risk factors. We believe prevention and early control of GVHD may contribute to this finding.

Partially mismatched related donor bone marrow transplantation as salvage for patients with AML who failed autologous stem cell transplant.

Treatment options for patients who relapse are limited and the outcome is dismal. Between August 1993 and January 1999, 17 patients, median age 26 (4-44) years, underwent T cell depleted bone marrow transplant from partially mismatched related donors (PMRD), as a salvage for AML relapsing after an autograft. The median time from auto-transplant to relapse was 7 months (1.5-24) and the interval between transplants was 10 months (3-30). All patients had active leukemia at time of transplant. Donors were siblings (n = 8), parents (n = 2), daughters (n = 4) and others (n = 3), and 82% were > or = 2 major HLA antigen mismatched with the recipient. The conditioning therapy included total body irradiation in 14 patients and was busulfan-based in three. Graft-versus-host disease (GVHD) prophylaxis consisted of partial T cell depletion along with post-transplant immunosuppression. Median day to engraftment was 16 days (12-20). Acute GVHD was seen in six patients, and chronic GVHD in four of 13 surviving beyond 100 days. Ten patients died of non-relapse causes, at 1-588 (median 77) days. Two patients relapsed at 3 and 4 months. Five patients (29%) are surviving leukemia-free 42-84 months post transplant (median 68 months). A short interval between transplants was predictive of early relapse but not mortality. Age <18 and <2 organ toxicities were marginally predictive of better survival. We conclude that BMT from PMRD is a reasonable option for patients with refractory AML post autograft.

Haploidentical vs autologous hematopoietic stem cell transplantation in patients with acute leukemia beyond first remission.

This is a retrospective comparison of partially mismatched related donor transplantation (PMRDT) and autotransplantation (ABMT) in advanced acute leukemia. Patients underwent T-cell-depleted PMRDT (n=164) or ABMT (n=131) for acute myeloid leukemia (n=130) or acute lymphoblastic leukemia (n=165). Fewer PMRDT patients were in remission (29 vs 85%; P<0.0001). The 5-year cumulative incidence of transplant-related mortality (TRM) was 52% after PMRDT and 16% after ABMT (P<0.0001). The 5-year cumulative incidence of relapse was 32% after PMRDT and 54% after ABMT (P=0.006). The actuarial unadjusted 5-year disease-free survival (DFS) was 16% after PMRDT and 30% after ABMT. In Cox's regression analysis, PMRDT (P<0.0001) and age >15 years (P=0.002) were associated with higher TRM, active disease (P=0.0021), ABMT (P=0.0074) and male sex (P=0.011) with higher relapse, and age >15 years (P=0.0007) and PMRDT (P=0.047) with lower DFS. Amongst second remission patients, TRM was higher after PMRDT (P=0.0003), relapse was higher after ABMT (P=0.034), and 5-year DFS was comparable (32% ABMT and 25% PMRDT). ABMT, if feasible, may be preferable to PMRDT in advanced acute leukemia patients since lower relapse after PMRDT is offset by higher TRM. If an autograft is not feasible because of nonavailability of autologous cells or very advanced disease, PMRDT is a potential alternative.

Allogeneic transplantation from HLA-matched sibling or partially HLA-mismatched related donors for primary refractory acute leukemia.

Allogeneic transplantation is successful in a minority of patients with primary refractory acute leukemia (PRAL). An HLA-matched sibling donor (MSD) is available only in 30-40% of the patients, whereas a partially mismatched related donor (PMRD) is available for most. We compared the outcome of 24 MSD (median age 24 years) and 19 PMRD (median age 34 years; P = 0.04) allograft recipients with PRAL. All MSD patients received non-T cell-depleted marrow whereas all PMRD patients received partially T cell-depleted marrow. All evaluable PMRD patients and 90% of the evaluable MSD patients attained CR. Six patients in each group with recurrent/persistent disease died. Ten PMRD (3-year probability 70%) and 14 MSD (3-year probability 63%) patients died of treatment-related causes. At the last follow-up, three PMRD (18-50 months; 3-year probability 14%) and four MSD (20-166 months; 3-year probability 20%) patients were alive and well. We conclude that allogeneic transplantation is a viable therapeutic option for PRAL. PMRD transplantation is a reasonable alternative in patients with no MSD, and results in similar outcome. In terms of identifying a donor and harvesting cells, a PMRD transplant is significantly quicker than an unrelated donor transplant - a point of great practical importance in the setting of failed induction chemotherapy where time is of the essence.

Bone marrow transplantation from partially HLA-mismatched family donors for acute leukemia: single-center experience of 201 patients.

Between February 1993 and December 1999, 201 patients (1-59 years old, median 23) with acute leukemia (67% not in remission) underwent ex vivo T-cell-depleted (TCD) bone marrow transplants (BMT) from partially mismatched related donors (PMRD; 92% mismatched for 2-3 HLA A, B, DR antigens). Conditioning comprised total body irradiation, cyclophosphamide, cytarabine, etoposide, anti-thymocyte globulin (ATG), and methylprednisolone. Graft-versus-host disease (GVHD) prophylaxis comprised partial TCD with OKT3 (n=143) or T10B9 (n=58), steroids, ATG, and cyclosporine. The engraftment rate was 98%. The cumulative incidences of grades II-IV acute GVHD and chronic GVHD were 13 and 15%, respectively. The 5-year cumulative incidences of relapse and transplant-related mortality (TRM) were 31 and 51%, respectively. The actuarial 5-year overall survival (OS) and disease-free survival (DFS) probabilities were 19 and 18%, respectively. Patient age >15 years, active disease at transplant, donor age >25 years, and 3-antigen donor mismatch (host-versus-graft) affected the outcome adversely. The actuarial 5-year OS of four groups of patients identified based upon these risk factors was 39, 20, 13, and 0%, respectively (P<0.0001). We conclude that PMRD BMT is a potential treatment option for patients with high-risk acute leukemia who require an alternative donor transplant and fall into a group with a reasonable expected outcome.