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Hematopoietic stem cell transplantation (HCT) is a primary treatment for various inherited metabolic disorders (IMDs). Achieving stable and sustained engraftment while minimizing transplantation-related morbidity and mortality is critical to optimizing outcomes for IMDs. Traditional regimens have used myeloablative approaches, primarily busulfan and cyclophosphamide (BuCy), which is associated with significant regimen-related toxicity. Alternatively, reduced-toxicity regimens, such as busulfan and fludarabine (BuFlu), have been proposed to offer similar efficacy with reduced toxicities. We compared transplantation-related outcomes with BuCy-based and BuFlu-based conditioning in patients with IMDs. We retrospectively analyzed the University of Minnesota's transplantation database for patients with IMDs who underwent HCT using a BuCy (with alemtuzumab) or BuFlu (with antithymocyte globulin) preparative regimen between March 2008 and September 2017. Overall survival (OS), event-free survival (EFS), and incidence of neutrophil and platelet recovery were determined using standard definitions. Complications such as graft failure, sinusoidal obstruction syndrome, hemorrhagic cystitis, and respiratory failure were compared. Graft failure includes primary and secondary aplastic graft failure with and without autologous recovery. The incidence of viral infections post-transplantation in the 2 regimens was also determined. A total of 99 patients underwent HCT for IMDs during the study period. Sixty-four patients received BuCy conditioning, and the other 35 received BuFlu. Hurler syndrome (46%) and adrenoleukodystrophy (43%) were the most common IMDs, and umbilical cord blood was the most common graft source (74%). One-year OS was similar in the 2 groups (81.2% in BuCy versus 85.5% in BuFlu; P = .8), with an EFS of 75% versus 63%, respectively. The 2 groups also had similar incidences of grade III-IV acute GVHD (9% versus 6%; P = .5) and chronic GVHD (9% versus 7%; P = .67). Neutrophil and platelet recovery were similar in the 2 groups, with a significantly shorter duration of hospital stay noted in the BuFlu cohort (median, 21 days versus 34 days; P = .002). The cumulative incidence of graft failure was significantly higher in the BuFlu group (29% versus 14%; P = .08), as was the rate of second HCT (27% versus 3%; P = .001). The incidences of adenoviral infection (14% versus 0%; P = .02) and hemorrhagic cystitis (23% versus 3%; P = .01) were higher in the BuCy group. T cell engraftment occurred significantly sooner with BuCy conditioning until 1-year post-transplantation, but donor myeloid engraftment was similar in the 2 groups. Our data indicate that reduced-toxicity conditioning is associated with lower rates of infection and other transplantation-related complications but is concerning for a higher rate of graft failure in patients with IMDs. Alternate immunosuppressive agents and novel techniques should be considered to minimize toxicities and reduce complications., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Children with acute leukemia who relapse after hematopoietic cell transplantation (HCT) have few therapeutic options. We studied 251 children and young adults with acute myelogenous or lymphoblastic leukemia who underwent a second HCT for relapse after their first HCT. The median age at second HCT was 11 years, and the median interval between first and second HCT was 17 months. Most of the patients (n = 187; 75%) were in remission, received a myeloablative conditioning regimen (n = 157; 63%), and underwent unrelated donor HCT (n = 230; 92%). The 2-year probability of leukemia-free survival (LFS) was 33% after transplantation in patients in remission, compared with 19% after transplantation in patients not in remission (P = .02). The corresponding 8-year probabilities were 24% and 10% (P = .003). A higher rate of relapse contributed to the difference in LFS. The 2-year probability of relapse after transplantation was 42% in patients in remission and 56% in those in relapse (P = .05). The corresponding 8-year probabilities were 49% and 64% (P = .04). These data extend the findings of others showing that patients with a low disease burden are more likely to benefit from a second transplantation. Late relapse led to a 10% decrement in LFS beyond the second year after second HCT. This differs from first HCT, in which most relapses occur within 2 years after HCT., (Copyright © 2018. Published by Elsevier Inc.)

The purpose of this study was to determine the effect of a pretransplant cranial boost (CB) on post-transplant central nervous system (CNS) relapse and survival in acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) using a total body irradiation (TBI)-containing preparation regimen. Two hundred thirteen ALL patients were treated consecutively at our institution with allogeneic HSCT. Conditioning included TBI (1320 cGy in 8 fractions given twice daily) and cyclophosphamide (120 mg/kg) with or without fludarabine (75 mg/m 2 ). Patients were divided into 4 groups based on history of CNS disease and whether a CB was given. Of the 160 patients with no history of CNS disease, none received a CB (CNS-/CB-). Of the 53 patients with prior CNS disease, 41 had not received prior cranial irradiation. Thirty of these 41 received a CB of 900 to 1000 cGy in 5 daily fractions (CNS+/CB+), whereas the other 11 did not receive a CB because of physician preference (CNS+/CB-). The remaining 12 patients with prior CNS involvement had previously received cranial irradiation and thus were not candidates for a CB (CNS + PriorRT). Two-year CNS relapse risk, overall survival (OS), and disease-free survival (DFS) were calculated using Kaplan-Meier analysis. Seven patients experienced post-transplant CNS relapse: 4 in the CNS-/CB- group, 2 in the CNS+/CB- group, and 1 in the CNS + PriorRT group. None of the 30 patients who received a CB relapsed in the CNS. Two-year CNS relapse risk was 0% in the CNS+/CB+ group compared with 21% (95% CI, 0% to 45%) in the CNS+/CB- group (P = .03). Two-year OS and DFS did not differ between the groups. In conclusion, among ALL patients with prior CNS leukemia, there was a trend toward a reduced risk of post-transplant CNS relapse in patients who received a CB. However, the addition of a CB did not appear to have an impact on OS or DFS., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

We studied leukemia-free (LFS) and overall survival (OS) in children with acute myeloid (AML, n = 790) and acute lymphoblastic leukemia (ALL, n = 1096) who underwent transplantation between 2000 and 2010 and who survived for at least 1 year in remission after related or unrelated donor transplantation. Analysis of patient-, disease-, and transplantation characteristics and acute and chronic graft-versus-host disease (GVHD) was performed to identify factors with adverse effects on LFS and OS. These data were used to develop risk scores for survival. We did not identify any prognostic factors beyond 4 years after transplantation for AML and beyond 3 years for ALL. Risk score for survival for AML includes age, disease status at transplantation, cytogenetic risk group, and chronic GVHD. For ALL, the risk score includes age at transplantation and chronic GVHD. The 10-year probabilities of OS for AML with good (score 0, 1, or 2), intermediate (score 3), and poor risk (score 4, 5, 6, or 7) were 94%, 87%, and 68%, respectively. The 10-year probabilities of OS for ALL were 89% and 80% for good (score 0 or 1) and poor risk (score 2), respectively. Identifying children at risk for late mortality with early intervention may mitigate some excess late mortality., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

This Center for International Blood and Marrow Transplant Research report describes the use of hematopoietic stem cell transplantation (HSCT) in pediatric patients with cancer, 4408 undergoing allogeneic (allo) and3076 undergoing autologous (auto) HSCT in the United States between 2008 and 2014. In both settings, there was a greater proportion of boys (n = 4327; 57%), children < 10 years of age (n = 4412; 59%), whites (n = 5787; 77%), and children with a performance score ≥ 90% at HSCT (n = 6187; 83%). Leukemia was the most common indication for an allo-transplant (n = 4170; 94%), and among these, acute lymphoblastic leukemia in second complete remission (n = 829; 20%) and acute myeloid leukemia in first complete remission (n = 800; 19%) werethe most common. The most frequently used donor relation, stem cell sources, and HLA match were unrelated donor (n = 2933; 67%), bone marrow (n = 2378; 54%), and matched at 8/8 HLA antigens (n = 1098; 37%) respectively. Most allo-transplants used myeloablative conditioning (n = 4070; 92%) and calcineurin inhibitors and methotrexate (n = 2245; 51%) for acute graft-versus-host disease prophylaxis. Neuroblastoma was the most common primary neoplasm for an auto-transplant (n = 1338; 44%). Tandem auto-transplants for neuroblastoma declined after 2012 (40% in 2011, 25% in 2012, and 8% in 2014), whereas tandem auto-transplants increased for brain tumors (57% in 2008 and 77% in 2014). Allo-transplants from relatives other than HLA-identical siblings doubled between 2008 and 2014 (3% in 2008 and 6% in 2014). These trends will be monitored in future reports of transplant practices in the United States., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Hepatic veno-occlusive disease, or sinusoidal obstruction syndrome (VOD/SOS), is a serious and potentially fatal complication of conditioning for hematopoietic stem cell transplantation (HSCT) or of chemotherapy regimens alone. Defibrotide is a complex mixture of single-stranded polydeoxyribonucleotides that is approved in the United States for treating hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT and in the European Union, Israel, and South Korea for treating severe hepatic VOD/SOS post-HSCT. Defibrotide was previously available in the United States as an investigational drug through a treatment protocol (treatment IND) study. Interim results of that large, treatment IND study of patients with VOD/SOS and with or without multiorgan dysfunction (MOD; also known as multiorgan failure) are presented here. Defibrotide was administered i.v. at 6.25 mg/kg every 6 hours (25 mg/kg/day), with a recommended treatment duration of at least 21 days. Enrolled patients (n = 681) were diagnosed with VOD/SOS based on Baltimore or modified Seattle criteria or liver biopsy analysis. Among the 573 HSCT recipients, 288 (50.3%; 95% confidence interval [CI], 46.2% to 54.4%) were alive at day +100 post-HSCT. Day +100 survival for the pediatric (≤16 years) and adult (>16 years) subgroups was 54.5% (95% CI, 49.1% to 60.0%; n = 174 of 319) and 44.9% (95% CI, 38.8% to 51.0%; n = 114 of 254), respectively. In the MOD subgroup, 159 of 351 patients (45.3%; 95% CI, 40.1% to 50.5%) of patients were alive at day +100 post-HSCT. Treatment with defibrotide was generally well tolerated, and drug-related toxicities were consistent with previous studies. Adverse events were reported in 69.6% of safety-evaluable patients (399 of 573). Other than VOD/SOS and associated MOD symptoms, the most commonly reported treatment-emergent adverse event was hypotension (13.8%). Day +100 survival results observed in this trial were consistent with results seen in previous trials of defibrotide for VOD/SOS in adult and pediatric patients. These data support the potential benefit of defibrotide in treating a VOD/SOS patient population that includes those with and without MOD., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Sustained donor engraftment after allogeneic hematopoietic cell transplantation (HCT) converts to healthy donor hemoglobin synthesis and halts disease symptoms in patients with sickle cell disease and thalassemia major. A disease-free survival probability that exceeds 90% has been reported when HCT using an HLA-matched sibling donor is performed in young patients with low-risk disease or treatment-related risk factors. Alternate donor HCT and HCT in adults is performed infrequently because of a higher risk profile. Transplant-specific risks include conditioning regimen-related toxicity, graft-versus-host disease, graft rejection with marrow aplasia or disease recurrence, and infections associated with immunosuppression and delayed immune reconstitution. The magnitude of risk depends on patient age, clinical status of the underlying disease (eg, organ injury from vasculopathy and iron overload), donor source, and intensity of the conditioning regimen. These risks are commonly monitored and reported in the short term. Documenting very late outcomes is important, but these data are rarely reported because of challenges imposed by patient drop-out and insufficient resources. This report summarizes long-term follow-up results after HCT for hemoglobin disorders, identifies gaps in knowledge, and discusses opportunities for future investigations. This consensus summary will be followed by a second article detailing comprehensive long-term follow-up recommendations to aid in maintaining health in these individuals and identifying late complication risks that could facilitate interventions to improve outcomes., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Allogeneic hematopoietic stem cell transplantation has demonstrated efficacy for numerous inherited metabolic disorders (IMDs). Umbilical cord blood transplant (UCBT) is increasingly used as a graft source in IMDs, but little is known of the impact of cord blood unit (CBU)/recipient HLA allelic disparity on key outcomes following UCBT for IMD. We reviewed outcomes of 106 consecutive first, single UCBTs for IMD at the University of Minnesota with regard to CBU/recipient HLA allelic matching (HLA-A, -B, -C, and -DRB1). The median age at UCBT was 1 year, and 87 patients (82%) received myeloablative conditioning. Primary diagnoses were Hurler syndrome (41%), cerebral adrenoleukodystrophy (35%), metachromatic leukodystrophy/globoid cell leukodystrophy (9%), and other (16%). The 5-year overall survival (OS) for the entire cohort was 70% (95% confidence interval, 59% to 79%). Rates of severe acute and chronic graft-versus-host disease were low (6% for each). CBU/recipient HLA conventional matching was based on antigen-level matching at HLA-A and -B, and on allele-level matching at HLA-DRB1. Of 46 conventional matched UCBTs, 20 (43%) were mismatched at 1 or more alleles. Of 49 conventional 5/6 UCBTs, 30 (61%) were mismatched at ≥2 alleles and 19 (39%) were mismatched at ≥3 alleles. Within the 6/6 conventional match stratum, comparisons of key outcomes between allele-matched and allele-mismatched UCBT were as follows: 5-year OS, 88% versus 42% (P < .01); 1-year engrafted survival (ES) with ≥90% donor chimerism, 73% versus 60% (P = .33); graft failure, 8% versus 30% (P = .05); and transplantation-related mortality (TRM), 8% versus 30% (P = .04). For patients undergoing conventional 5/6 HLA-matched UCBT, better allelic matching was associated with similar outcomes: 5-year OS, 77% versus 74% (P = .72); 1-year ES, 73% versus 47% (P = .06); graft failure, 17% versus 42% (P = .05); and TRM, 10% versus 16% (P = .54). On multivariable analyses, fewer allele-level mismatches within each conventional match stratum continued to predict more favorable outcomes following UCBT. These data provide evidence that allele-level HLA matching considerations within a conventional HLA match stratum may better predict outcomes of interest after UCBT for IMD. Larger studies are warranted to confirm these findings and explore other allele-level HLA match dynamics., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Existing literature shows mixed conclusions regarding the impact of ABO incompatibility on outcomes after hematopoietic stem cell transplantation. Because the future for umbilical cord blood (UCB) expansion technologies is bright, we assessed whether this typically overlooked graft characteristic impacted various outcomes after UCB transplantation (UCBT) for nonmalignant disorders (NMDs). A prospectively maintained institutional blood and marrow transplant program database was queried for all patients undergoing first UCBT for NMDs. UCB and recipient ABO compatibility was considered as matched, major mismatched, minor mismatched, or bidirectional mismatched. The impact of ABO incompatibility was assessed on overall survival, graft failure, acute and chronic graft-versus-host disease (GVHD), time to neutrophil and platelet recovery, day 0 to day 100 RBC transfusion burden, and donor hematopoietic chimerism. Through December 2014, 270 patients have undergone first UCBT for various NMDs. In both univariable and multivariable analyses, ABO compatibility status did not appear to impact any outcomes assessed, although a trend toward increased grades III to IV acute GVHD was seen in recipients of major mismatched units. When considering UCBT for treatment of NMDs, ABO compatibility between the donor unit and intended recipient does not appear to be an important consideration in the UCB unit choice., Competing Interests: There are no conflicts of interest to report., (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Acute kidney injury (AKI) is a well-documented complication of pediatric hematopoietic stem cell transplantation (HSCT). Dialysis after HSCT is associated with a lower overall survival (OS); however, the association between less severe AKI and OS is unclear. We retrospectively studied 205 consecutive pediatric HSCT patients to determine the incidence and impact of all stages of AKI on OS in pediatric HSCT recipients. We used the peak pRIFLE grade during the first 100 days to classify AKI (ie, R = risk, I = injury, F = failure, L = loss of function, E = end-stage renal disease) and used the modified Schwartz formula to estimate glomerular filtration rate. AKI was observed in 173 of 205 patients (84%). The 1-year OS rate decreased significantly with an increasing severity of pRIFLE grades (P < .01). There was no difference in the OS between patients without AKI and the R/I group. Regardless of the dialysis status, stages F/L/E had significantly lower rates of OS compared with patients without AKI or R/I (P < .01). There was no difference in OS among patients with dialysis and F/L/E without dialysis (P = .65). Stages F/L/E predicted mortality independent of acute graft-versus-host disease, gender, and malignancy. The OS of children after HSCT decreases significantly with an increasing severity of AKI within the first 100 days post-transplant. Although our data did not show an increased risk of mortality with stages R/I, stages F/L/E predicted mortality regardless of dialysis. Prevention and minimization of AKI may improve survival after pediatric HSCT., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Allogeneic hematopoietic stem cell transplantation for patients with a hemoglobinopathy can be curative but is limited by donor availability. Although positive results are frequently observed in those with an HLA-matched sibling donor, use of unrelated donors has been complicated by poor engraftment, excessive regimen-related toxicity, and graft-versus-host disease (GVHD). As a potential strategy to address these obstacles, a pilot study was designed that incorporated both a reduced-intensity conditioning and mesenchymal stromal cells (MSCs). Six patients were enrolled, including 4 with high-risk sickle cell disease (SCD) and 2 with transfusion-dependent thalassemia major. Conditioning consisted of fludarabine (150 mg/m(2)), melphalan (140 mg/m(2)), and alemtuzumab (60 mg for patients weighing > 30 kg and .9 mg/kg for patients weighing <30 kg). Two patients received HLA 7/8 allele matched bone marrow and 4 received 4-5/6 HLA matched umbilical cord blood as the source of HSCs. MSCs were of bone marrow origin and derived from a parent in 1 patient and from an unrelated third-party donor in the remaining 5 patients. GVHD prophylaxis consisted of cyclosporine A and mycophenolate mofetil. One patient had neutropenic graft failure, 2 had autologous hematopoietic recovery, and 3 had hematopoietic recovery with complete chimerism. The 2 SCD patients with autologous hematopoietic recovery are alive. The remaining 4 died either from opportunistic infection, GVHD, or intracranial hemorrhage. Although no infusion-related toxicity was seen, the cotransplantation of MSCs was not sufficient for reliable engraftment in patients with advanced hemoglobinopathy. Although poor engraftment has been observed in nearly all such trials to date in this patient population, there was no evidence to suggest that MSCs had any positive impact on engraftment. Because of the lack of improved engraftment and unacceptably high transplant-related mortality, the study was prematurely terminated. Further investigations into understanding the mechanisms of graft resistance and development of strategies to overcome this barrier are needed to move this field forward., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

It is not unusual for children to require dialysis for fluid and electrolyte management after hematopoietic cell transplantation (HCT). Previous studies have documented high mortality in children who require dialysis after HCT, but recent data are lacking. The purpose of this study was to compare the incidence of dialysis after pediatric HCT and the survival of patients who received dialysis in 2 decades, 1990-1999 and 2000-2009. A total of 1427 patients age <21 years who underwent a first HCT at the University of Minnesota between January 1990 and December 2009 were reviewed using prospectively collected data from the institutional HCT database. The incidence of dialysis during the first 100 days post-HCT and survival at 1 year post-HCT in the 2 cohorts were determined. Comparisons between patients who did and did not require dialysis were made using the χ(2) and Fisher exact tests as appropriate. Kaplan-Meier estimates and 95% confidence intervals for 1-year post-HCT overall survival were reported by dialysis group and compared using the log-rank test. Predictors of overall survival among patients requiring dialysis were assessed using univariate and multivariate Cox regression analyses. The incidence of dialysis was not significantly different in the 2 cohorts (8.2% for 1990-1999 versus 8.9% for 2000-2009; P = .6326). Patients requiring dialysis were significantly more likely to survive to or past 1 year in the 2000-2009 cohort compared with the 1990-1999 cohort (23% versus 11%; P < .0001). Multivariate analyses found that older age at the time of HCT, primary disease type, pulmonary hemorrhage, and HCT in 1990-1999 were associated with increased mortality in the dialyzed population. The use of cyclosporine was associated with increased survival in the patients who received dialysis. Dialysis is an important complication of pediatric HCT with an incidence that has remained constant over the last 2 decades. Survival was improved in the 2000-2009 cohort regardless of dialysis status. Despite a recent significant reduction in mortality in patients requiring dialysis, mortality remains higher in these patients than in those who do not need dialysis., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Risk-adapted therapy has been the cornerstone of treatment for pediatric B precursor acute lymphoblastic leukemia (B-ALL). Recently, age ≥ 13 years at diagnosis has been identified as a very high-risk feature for chemotherapy treated pediatric patients with B-ALL. Whether age at time of transplantation is associated with poor outcomes in adolescents and young adults (AYA) is unknown. We hypothesized that AYA receiving allogeneic hematopoietic cell transplantation (allo-HCT) would have greater relapse and inferior survival compared with children age <13 years. We reviewed the outcomes in 136 consecutive patients (age 0-30 years) with B-ALL who underwent myeloablative allo-HCT at our institution, including 79 children age <13 years (58%) and 57 AYA age 13-30 years (42%). Overall survival at 5 years was significantly lower in the AYA group (hazard ratio, 1.74; 95% confidence interval [CI], 1.04-2.95; P = .03). In addition, the AYA patients had a greater risk of transplantation-related mortality at 1 year (hazard ratio, 2.23; 95% CI, 1.01-4.90; P = .05), but no difference in relapse (relative risk, 0.85; 95% CI, 0.41-1.76; P = .66). Based on this analysis, AYA patients undergoing allo-HCT for B-ALL have significantly inferior survival and greater transplantation-related mortality compared with children age <13 years, but no difference in relapse, suggesting that allo-HCT may overcome relapse in AYA. Further improvements in peritransplantation care are needed to limit complications in AYA patients., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Human parainfluenza viruses (HPIVs) are uncommon, yet high-risk pathogens after hematopoietic stem cell transplant (HCT). We evaluated 5178 pediatric and adult patients undergoing HCT between 1974 and 2010 to determine the incidence, risk factors, response to treatment, and outcome of HPIV infection as well as any change in frequency or character of HPIV infection over time. HPIV was identified in 173 patients (3.3%); type 3 was most common (66%). HPIV involved upper respiratory tract infection (URTI; 57%), lower respiratory tract infection (LRTI; 9%), and both areas of the respiratory tract (34%), at a median of 62 days after transplantation. In more recent years, HPIV has occurred later after HCT, whereas the proportion with nosocomial infection and mortality decreased. Over the last decade, HPIV was more common in older patients and in those receiving reduced intensity conditioning (RIC). RIC was a significant risk factor for later (beyond day +30). HPIV infections, and this association was strongest in patients with URTI. HCT using a matched unrelated donor (MURD), mismatched related donor (MMRD), age 10 to 19 years, and graft-versus-host disease (GVHD) were all risk factors for HPIV infections. LRTI, early (<30 days), age 10 to 19 years, MMRD, steroid use, and coinfection with other pathogens were risk factors for mortality. The survival of patients with LRTI, especially very early infections, was poor regardless of ribavirin treatment. HPIV incidence remains low, but may have delayed onset associated with RIC regimens and improving survival. Effective prophylaxis and treatment for HPIV are needed., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Rapid lymphocyte recovery after bone marrow or peripheral blood transplantation is associated with improved survival. However, the impact of early lymphocyte recovery has not been examined after umbilical cord blood transplant (UCBT). We evaluated lymphocyte recovery in 360 consecutive patients with hematologic malignancy that underwent UCBT between 2001 and 2007. Uniform myeloablative (MA), reduced intensity conditioning (RIC) and graft-versus-host disease prophylaxis regimens were used. In multivariate analysis, an absolute leukocyte count (ALC) >200 × 10(6)/L at day 30 (n = 73) after MA conditioning was associated with superior 2-year overall survival (OS) (73% versus 61%; P = .02) (relative risk [RR]: 2.29; 95% confidence interval [CI]: 1.15-4.56), progression-free survival (PFS) (68% versus 54%; P = .05) (RR: 1.96; 95% CI: 0.99-3.86) and less transplant-related mortality (8% versus 28%, P < .01) (RR: 4.38; 95% CI: 1.65-11.60) compared to ≤200 × 10(6)/L (n = 43). Similarly, an ALC >200 × 10(6)/L at day 42 (n = 105) after RIC was associated with superior 2-year OS (59% versus 41%, P < .01) (RR: 2.10; 95% CI: 1.3-3.41) and PFS (46% versus 36%, P = .05) (RR: 1.58; 95% CI: 1.01-2.49) compared to ≤200 × 10(6)/L (n = 55). There was no significant relationship between ALC and relapse. Rapid lymphocyte recovery early after UCBT predicts better survival in patients with hematologic malignancies., (Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Transplant decisions for children with acute lymphoblastic leukemia (ALL) in second complete remission (CR2) are often based on the type of available donor. In many cases, allogeneic hematopoietic cell transplantation (HCT) is considered only if a human leukocyte antigen (HLA) matched sibling donor (MSD) is available. The role of unrelated donor (URD) HCT in this patient population is not well established. As advances in supportive care and donor selection have improved, the use of URD HCT in such patients should be reevaluated. We analyzed the outcomes of 87 consecutive children with ALL in CR2 who underwent allogeneic HCT at the University of Minnesota between 1990 and 2007. Donor sources included MSD bone marrow (n = 32), well and partially matched (M, n = 18) and mismatched (MM, n = 16) URD bone marrow and URD umbilical cord blood (UCB, n = 21). Although the incidence of neutrophil recovery was similar in all groups, the overall incidence of grades II-IV acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) was 37% and 9%, respectively, with a higher incidence of aGVHD in recipients of URD grafts. Leukemia-free survival (LFS) at 5 years was lower in recipients of MM-URD grafts, but was comparable in all other groups. Although relapse at 5 years was highest in recipients of MSD (50%), results were not significantly different compared to recipients of M-URD (17%), MM-URD (6%), and UCB (33%) (P = .17). The development of grades II-IV aGVHD and a first remission >3 years were associated with a lower risk of relapse (relative risk [RR] 0.2, P = .03; RR 0.2. P = .01 respectively). Together, these results support the continued investigation of URD HCT for ALL in CR2, and suggest the timing of HCT in these children should be based primarily on the risk of relapse with conventional chemotherapy and not on the type of donor available.