Hale, Gregory A.

Abstract Few data are available on the outcomes of patients who fail to engraft following URD transplantation. We describe the results of 122 patients reported to the National Marrow Donor Program (NMDP) between 1990 and 2005, who received a second bone marrow (BM) or peripheral blood (PB) URD transplant after failing to achieve an absolute neutrophil count of ≥ 500/mm3 without evidence of recurrent disease. Patients were transplanted for leukemia (n=83), myelodysplastic disorders (n=16), severe aplastic anemia (n=20) and other disease (n=3). The median age at first transplant was 29 years. Approximately one third were in each age range, < 20 (33%), 20–40 (37%) and >40 (29%). The initial transplant was BM in 84% of patients while 51% received BM for the subsequent transplant. One hundred ten of these patients received two transplants, 11 received three and one received 4 transplants. Twenty four used a different donor whereas 98 used the original donor for the second transplant; 28 of these used cells that had been cryopreserved at the initial transplant date. Nearly two thirds of the patients received reduced intensity conditioning or no conditioning for the second transplant. Sixty one percent had ATG as a component of their second transplant. The median interval from first transplant to second transplant was 48 (range, 18–126) days. The median nucleated cell dose was 2 × 108/kg (range, <1–23) for the first transplant and 2 × 108/kg (range, <1–50) for the second. The median follow up of survivors after second transplant was 77 (range, 2–144) months. Univariate probabilities of outcomes for these patients after second transplant were: Outcome N eval Probability (95% CI) *cumulative incidence Neutrophil engraftment* 122 @ 28 days 43 (34–52) % @100 days 48 (39–57) % 30 day mortality 122 39 (31–48) % 100 day mortality 122 75 (67–82) % Overall survival (OS) @ 1 year 122 11 (6–17) % Treatment related mortality (TRM) @ 1 year* 99 86 (79–92) % Disease free survival (DFS) @ 1 year 99 7 (2–12) % Of the 122 patients analyzed, only 10 remain alive. The most common causes of death were graft failure or rejection (33%), organ failure/interstitial pnuemoniatis (22%), infection (15%), GVHD (14%) and recurrent disease (6%). Of the 37 patients who had persistent graft failure 21 (57%) died from infectious causes. We observed no differences between patients who received a graft from the same donor vs. different donor, fresh vs. cryopreserved cells, or small initial graft size vs. large initial graft size. Patients who received a T-cell depleted graft at the time of their first transplant had significantly worse survival at 1 year after their second transplant, 4% (95% CI, 0–11) compared to those patients who had a non T-cell depleted initial graft, 16% (95 % CI, 8–25)(P = 0.02). It appears that a second salvage transplant strategy may be effective in a small group of patients, although the overall DFS at 1 year of only 7% is disappointing. To improve these results, efforts might focus on early identification and treatment of those at highest risk for non engraftment to determine whether such a strategy can alter the natural history we have described.

Abstract Background: Myeloablative hematopoietic cell transplantation (HCT) provides a cure for children with hemoglobinopathies, but transplant related early and late morbidity remains a challenge. Toxicities associated with myeloablative chemotherapy include early complications such as mucositis, hemorrhagic cystitis, seizures, and hepatic injury. Late effects such as infertility and compromised linear growth impair long-term quality of life, often decreasing enthusiasm for the procedure. Reduced intensity preparative regimens are especially attractive in children with non-malignant disorders to mitigate these toxicities but have been associated with increased risk of graft rejection. The primary objective of this study was to determine the toxicity and efficacy of a non-myeloablative preparative regimen using alemtuzumab, fludarabine, and melphalan followed by HCT from HLA matched related donors (MRD) in children with hemoglobinopathies. Methods: Following institutional review board approval, and parent and/or patient consent, participants were enrolled at 18 centers. Children < 21 years of age with severe sickle cell disease (SCD) manifestations, or transfusion dependent (> 8 red blood cell transfusions per year) thalassemia with a MRD and a performance status > 40 were eligible for inclusion. The preparative regimen included alemtuzumab (total dose 48 mg) IV (between days –22 and –19), fludarabine (30 mg/m2/day) (days –8 to –4) and melphalan (140 mg/m2) on day -3. Graft versus host disease (GVHD) prophylaxis included a calcineurin inhibitor (tapered after day 100, and methotrexate (7.5 mg/m2 on days 1, 3 and 6) or mycophenolate mofetil. Five patients also received methylprednisone (1 mg/kg/day) between days 1 and 28; this practice was discontinued in 2007. Results: A total of 52 children (43 with SCD and 9 with thalassemia), median age 11 years (range, 10m - 20y) underwent HCT between March 2003 and July 2014. Of these, 46 received bone marrow, 5 received marrow and cord blood (CB), and 1 received CB alone. Median follow up was 35.5 months (range, 3 – 136). Forty-nine children were alive at last follow up (Figure 1); 48 were symptom-free; one CB recipient had disease recurrence following graft rejection and successfully underwent a 2nd HCT. No hepatic veno-occlusive disease was noted. Three deaths 6, 11 and 21 months post HCT were from GVHD related causes [bronchiolitis obliterans (n=1); infection with GVHD (n=2)]. The cumulative incidence of graft failure and transplant related mortality was 1.9% and 5.7% respectively. The mean time to engraftment of neutrophils (ANC >500/cu mm) and platelets (>50,000/cu mm) was 13.0 (range 5-21) and 25.9 (range 8-120) days respectively. Three patients had neurologic toxicity (seizures/PRES) post HCT. At the time of last follow up, 35 patients (67%) were complete donor chimera (>90% donor) and 16 (31%) were mixed chimera (28-89% donor). Acute GVHD (grade 1-3) was noted in 30.8%. Four had grade I, 6 had grade II, and 6 had grade III GVHD. No patient developed grade IV aGVHD. Chronic GVHD was noted in 13%. Of 43 patients that were alive without disease and >6 months post HSCT, 38 had successfully discontinued all immune suppression and maintained donor chimerism post withdrawal. Immune reconstitution was robust by the end of the first year post transplant; infectious complications (23 of 30 CMV+ recipients had reactivation) were noted primarily in the first 3 months post HSCT. Conclusions: Children with hemoglobinopathies undergoing MRD HCT tolerated this non-myeloablative preparative regimen well, with minimal early toxicities. The event-free survival rate was comparable to those achieved with myeloablative regimens. Withdrawing immunosuppression was not associated with graft loss or recurrent GVHD. GVHD complications resulted in a low mortality rate. Alternative GVHD prophylaxis may further improve event-free survival. No gonadal toxicity (determined by hormone levels) has been identified to date in 15 HCT recipients of pubertal age (>13 years). Follow up however is early and in progress to determine long-term toxicities. These results support consideration of reduced intensity conditioning regimens for HCT in children with hemoglobinopathies as an alternative to standard myeloablative regimens. Figure 1: Overall/Event-free survival following non-myeloablative conditioning andMRD transplants for hemoglobinopathy Figure 1:. Overall/Event-free survival following non-myeloablative conditioning andMRD transplants for hemoglobinopathy Disclosures No relevant conflicts of interest to declare.

Abstract Background Denintuzumab mafodotin (SGN-CD19A) is an antibody-drug conjugate (ADC) composed of a humanized anti-CD19 monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin F (MMAF) via a maleimidocaproyl linker. CD19 is a B cell-specific marker that is expressed in nearly all patients (pts) with B-lineage acute leukemia or lymphoma. Methods A phase 1 dose-escalation study is ongoing to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of denintuzumab mafodotin in pts with relapsed or refractory (R/R) B-ALL, B-cell lymphoma (B-LBL), or Burkitt leukemia/lymphoma (NCT 01786096). Eligible pts are ≥1 year of age and are R/R to ≥1 prior systemic regimen; patients with Philadelphia chromosome-positive (Ph+) disease must have failed a 2nd-generation TKI. A modified continual reassessment method was used for dose allocation and maximum tolerated dose (MTD) estimation. The study evaluated 2 dosing schedules: first weekly (Days 1 and 8 of 21-day cycles) and then once every 3 weeks (q3wk). This report presents data from the adult subset of pts in the study (≥18 years). Results To date, 71 adult pts with R/R B-ALL (n=59), B-LBL (n=6) or Burkitt leukemia/lymphoma (n=6) have been treated; median age is 45 years (range 18−77). Pts received a median of 2 prior therapies (range 1−8); 20 pts (28%) had prior allogeneic stem cell transplant. On the weekly schedule (0.3−3 mg/kg), 40 pts received a median of 2 cycles (range 1−27); 2 pts remain on treatment. On the q3wk schedule (4−6 mg/kg), 31 pts received a median of 3 cycles (range 1−6); 4 pts remain on treatment. An MTD was identified at 5 mg/kg q3wk and was not reached with weekly dosing. Best clinical responses to date for pts with B-ALL are summarized below: Table 1.Response category per Cheson 2003Efficacy-evaluable adult pts with B-ALLweekly dosing, N=32 n (%)q3wk dosing, N=23 n (%)Complete remission (CR)6 (19)3 (13)CR with incomplete platelet recovery (CRp)−3 (13)CR with incomplete blood recovery (CRi)−2 (9)Partial remission (PR)1 (3)−Resistant disease with clinical benefit15 (47)12 (52)Resistant disease without clinical benefit2 (6)-Progression8 (25)3 (13)CRc (CR+CRi+CRp), % (95% CI)19% (95% CI 7, 36)35% (95% CI 16, 57) In the q3wk schedule, the CRc rate was similar at 4, 5, and 6 mg/kg. The median duration of response across schedules is currently 27 weeks (95% CI 7, −). Of 12 pts with CRc and available minimal residual disease (MRD) assessment, 7 were MRD negative. 3 patients with MRD-negative CRs have been in remission for >1 year, 2 of whom have been on continuous treatment for 19 and 22 months. In the subset of pts with Ph+ B-ALL, 4 of 8 pts achieved CR and 1 pt a PR. In 6 pts with Burkitt leukemia/lymphoma, 1 achieved a CR. In 6 pts with B-LBL, objective responses were 1 CR and 2 PR. The adverse event (AE) profiles were similar across both dosing schedules; the most frequently reported AEs were pyrexia (54%), nausea (52%), fatigue (51%), headache (44%), chills (38%), vomiting (37%), blurred vision (35%), and anemia (34%). Ocular symptoms and corneal exam findings consistent with superficial microcystic keratopathy were observed in 40 pts (56%); symptoms were less severe than the associated corneal exam findings. Keratopathy was managed with topical steroids and dose modifications, and improved/resolved within a median of ~3 wks (range 1-17) in pts with sufficient follow-up. ADC exposures increased with dose, and in leukemia patients, target-mediated disposition was observed that diminished with higher doses in the q3wk schedule. Post treatment, flow cytometry data demonstrate that unbound CD19 on peripheral blasts inversely correlates with ADC concentration in circulation, and is present in the majority of evaluable patients at the end of the q3wk cycle. Conclusions Denintuzumab mafodotin is generally well tolerated and demonstrates activity in heavily pretreated adult pts with B-ALL and B-lineage highly aggressive lymphomas, including durable MRD-negative responses. The results of this trial indicate that the q3wk schedule, with a CRc rate of 35% in B-ALL, warrants further clinical investigation. Based on the encouraging responses observed to date in Ph+ B-ALL (CRs in 4 of 8 pts), an expansion cohort of these pts is currently enrolling on the q3wk schedule. Disclosures Fathi: Exelexis: Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Consultancy; Takeda Pharmaceuticals International Co.: Research Funding. Off Label Use: SGN-CD19A is an investigational agent being studied in patients with B-cell malignancies. SGN-CD19A is not approved for use.. Borate:Seattle Genetics: Research Funding; Genoptix: Consultancy; Alexion: Speakers Bureau; Gilead: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Speakers Bureau. DeAngelo:Agios: Consultancy; Incyte: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy; Ariad: Consultancy; Novartis: Consultancy. O'Brien:Seattle Genetics, Inc.: Research Funding. Trippett:OSI Pharmaceuticals: Research Funding; Seattle Genetics, Inc.: Research Funding. Shah:NCCN: Consultancy; SWOG: Consultancy; Seattle Genetics: Research Funding; Acetylon Pharmaceuticals, INC: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Speakers Bureau; Bayer: Honoraria; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Speakers Bureau; DeBartolo Institute for Personlaized Medicine: Research Funding; Rosetta Genomics: Research Funding; Plexus Communications: Honoraria; Spectrum: Speakers Bureau. Hale:Seattle Genetics, Inc.: Research Funding; Hyundai: Research Funding; V Foundation: Research Funding. Silverman:Seattle Genetics, Inc.: Research Funding. Pauly:Seattle Genetics, Inc.: Research Funding. Kim:Bayer: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Eli Lilly: Consultancy. Kostic:Seattle Genetics, Inc.: Employment, Equity Ownership. Huang:Seattle Genetics, Inc.: Employment, Equity Ownership. Pan:Seattle Genetics, Inc.: Employment, Equity Ownership. Chen:Genentech: Consultancy, Speakers Bureau; Seattle Genetics, Inc.: Consultancy, Other: Travel expenses, Research Funding, Speakers Bureau; Millennium: Consultancy, Research Funding, Speakers Bureau.

Abstract Background CD19, a B cell-specific marker, is expressed in the majority of patients with B-lineage leukemia and non-Hodgkin lymphoma. SGN-CD19A is a novel antibody-drug conjugate (ADC) composed of a humanized anti-CD19 monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin F (MMAF) via a maleimidocaproyl linker. Methods This first-in-human, phase 1, open-label, dose-escalation study is investigating the safety, tolerability, pharmacokinetics, and antitumor activity of SGN-CD19A in adult and pediatric patients with relapsed or refractory B-cell leukemia or highly aggressive lymphoma (NCT 01786096). Eligible patients must have B-cell acute lymphoblastic leukemia (B-ALL) or lymphoma (B-LBL), Burkitt leukemia or lymphoma, and be relapsed or refractory to at least 1 prior systemic regimen. A modified continual reassessment method is used for dose allocation and maximum tolerated dose (MTD) estimation for both pediatric and adult patients. The study is evaluating 2 schedules of IV SGN-CD19A administration: weekly (Days 1 and 8 of 21-day cycles; 0.3-4.5 mg/kg) or every 3weeks (q3week; 0.5-6 mg/kg). Results To date, 49 patients with relapsed or refractory leukemia (n=40) or lymphoma (n=9) have been treated. Median age of adult (n=38) and pediatric patients (n=11) was 37 and 11 years (range, 18-74 and 1-16), respectively. Patients received a median of 2 prior therapies (range 1-9); 14 patients (29%) previously received an allogeneic stem cell transplant. On the weekly schedule, 39 patients (28 adult, 11 pediatric) have been treated, and the median number of cycles is 2.5 (adults; range, 1-12) or 1 (pediatric; range, 1-4). On the q3week schedule, 10 adult patients have been treated, and the median number of cycles is 2.5 (range, 1-4) to date. Six patients remain on study treatment (3 on each schedule), and enrollment is ongoing. The toxicity profiles were similar across both dosing schedules (0.3-2.3 mg/kg weekly and 4-5 mg/kg q3week) and across adult and pediatric patients. The most frequently reported drug-related AEs included pyrexia, nausea, chills, vomiting, blurred vision, and dry eye. Frequent infusion-related reactions were observed early in the study, and recommendation for premedication was instituted. Ocular events were also observed and treated with ophthalmic steroids; steroid eye drop prophylaxis was instituted with each dose. Corneal findings consistent with superficial microcystic keratopathy were observed in 13 adult patients (34%) and in 1 pediatric patient (9%). Grade 3/4 corneal AEs have been observed in 4 adult patients; the majority of these events have resolved or improved to Grade 1 or 2. Steroid eye drop prophylaxis has reduced the incidence of Grade 3/4 events at this interim analysis. Three DLTs were observed: acidosis in a pediatric patient at 1 mg/kg weekly, cytokine release syndrome in an adult patient at 2 mg/kg weekly, and asymptomatic Grade 4 AST elevation in an adult patient at 5 mg/kg q3week. MTD has not yet been determined. SGN-CD19A ADC pharmacokinetic profiles indicate target-mediated drug disposition in patients with leukemia. Plasma ADC exposures generally increased with doses and were lower than those in patients with lymphoma. To date, no objective responses were observed in 9 efficacy-evaluable pediatric patients or in 3 adult patients with Burkitt lymphoma/leukemia. However, in efficacy-evaluable adult patients with B-ALL/B-LBL, objective responses were observed in 6 of 25 patients treated on the weekly schedule (3 CR, 2 CRp, 1 PR), and in 4 of 8 patients treated on the q3week schedule (2 CR, 2 CRp). Of 8 B-ALL patients with CR/CRp, 6 were MRD negative. Conclusions MTDs have not yet been identified, and dose escalation continues on weekly and q3week schedules. SGN-CD19A has been generally well tolerated. At this interim analysis, objective responses were observed in 30% (10 of 33) of heavily pretreated adult B-ALL/B-LBL patients dosed weekly or q3week. Evidence of activity in relapsed/refractory patients and lack of overlapping toxicities suggest opportunities for combination with conventional anti-leukemic therapies in lymphoblastic malignancies. Disclosures Fathi: Ariad: Consultancy; Exelixis: Research Funding; Takeda pharmaceuticals International Co.: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding. Off Label Use: SGN-CD19A is an investigational agent being studied in patients with B-cell malignancies. SGN-CD19A is not approved for use. . Chen:Seattle Genetics, Inc.: Consultancy, Research Funding, Speakers Bureau, Travel expenses Other. Trippett:OSI Pharmaceuticals: Research Funding; Seattle Genetics, Inc.: Research Funding. O'Brien:Seattle Genetics, Inc.: Research Funding. DeAngelo:Seattle Genetics, Inc.: Research Funding. Shah:Pharmacyclics: Consultancy; SWOG: Consultancy; Celgene: Consultancy, Speakers Bureau; NCCN: Consultancy; Seattle Genetics, Inc.: Research Funding; Janssen: Consultancy. Cooper:Seattle Genetics, Inc.: Research Funding. Foran:Seattle Genetics, Inc.: Research Funding. Hale:Seattle Genetics, Inc.: Research Funding. Pressey:Seattle Genetics, Inc.: Research Funding. Silverman:Seattle Genetics, Inc.: Research Funding. Tibes:Seattle Genetics, Inc.: Research Funding. Kim:Bayer: Consultancy; Eli Lily: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding. Albertson:Seattle Genetics, Inc.: Employment, Equity Ownership. Sandalic:Seattle Genetics, Inc.: Employment, Equity Ownership. Zhao:Seattle Genetics, Inc.: Employment, Equity Ownership. Borate:Genoptix: Consultancy; Seattle Genetics, Inc.: Research Funding.

Abstract Background: The association of clinical trial participation with outcomes in cancer patients is controversial, with some studies reporting better outcomes for trial participants while others do not. It is possible that the difference in outcomes is due to differences in baseline characteristics of participants and non-participants. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 trial was a large randomized, multi-center study comparing peripheral blood (PB) with bone marrow (BM) for hematopoietic cell transplantation (HCT) from HLA-matched or 1 allele mismatched unrelated donors (URD) in patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndromes. The trial reported no significant survival differences between PB and BM; there was decreased risk of graft failure but increased risk of chronic graft-versus-host disease (GVHD) with PB grafts (Anasetti et al NEJM 2012). Methods: We compared characteristics of BMT CTN 0201 study participants (n=494) with HCT recipients who did not participate on the trial (n=1384) but were potentially eligible by virtue of known characteristics. These patients received similar conditioning and GVHD prophylaxis as trial participants at 38 United States trial centers during the study time-period. Centers that had no eligible non-trial participants were excluded. Outcomes between patients on and off trial were compared using Cox proportional hazards regression models. Data were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) that collects patient data on all trial and non-trial allogeneic HCT recipients through its registry function. Results: Approximately 29% [494/1878] of apparently eligible patients were randomized and analyzed as part of the trial. There were no significant differences between study participants and non-participants in age or sex distribution, disease types, HLA or sex matching, comorbidities, or interval from diagnosis to HCT. Higher proportions of non-participants were Hispanic, had a lower performance status and lower disease risk, and received myeloablative conditioning and antithymocyte globulin (ATG) or Campath than the study participants. PB was used more commonly as the graft source in the non-participants as compared to the study participants (65% vs. 50%, p<0.001). In multivariate models, overall mortality (HR 1.09, 95% CI 0.95-1.25, p=0.22), transplant-related mortality (HR 1.08, 95% CI 0.89-1.32, p=0.42) and risks of acute grade II-IV (HR 0.96, 95% CI 0.82-1.12, p=0.57) and chronic GVHD (HR 1.06, 95% CI 0.92-1.23, p=0.41) were comparable between study non-participants and participants. Non-participants were at higher risk for relapse than participants (HR 1.24, 95%CI 1.04-1.49, p=0.02) in the multivariate analysis adjusted for disease risk and other clinical variables. Center effect was examined and was not found to be significant (p=0.10). There was no significant interaction between graft source and trial participation (P=0.22) and the risk of mortality was comparable for BM (HR 0.99, 95% CI 0.80-1.22, p=0.90) and PB recipients (HR 1.17, 95% CI 0.97-1.41, p=0.09) whether on trial or off trial. (Figure) Conclusion: Approximately 29% of patients who appeared eligible and were treated with conditioning and GVHD prophylaxis regimens allowed on the trial were enrolled. Despite some differences in clinical characteristics, most of the outcomes of non-trial participants were comparable to trial participants, suggesting that there is no definitive evidence that the outcomes of patients in a clinical trial are superior to those of the non-participants treated in a similar fashion. The comparable outcomes also indicate that the results of this trial were not seriously affected by selection bias and are therefore representative of the larger population. Figure 1: Adjusted overall survival in BMT CTN 0201 trial participants and non-participants Figure 1:. Adjusted overall survival in BMT CTN 0201 trial participants and non-participants Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Abstract Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT). Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research. Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P &lt; 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P &lt; 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or ≥5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P &lt; 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years). Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.

Key Points Compared with parous female sibling donors, male URDs confer more aGVHD in all patients and more cGVHD in females. There was no difference in survival, relapse, or transplant mortality between recipients of parous female sibling or male URD grafts.

Key Points In combination with cyclophosphamide, intravenous busulfan is associated with better leukemia-free and overall survival in AML than TBI.