Two-year Probabilities Research Articles

Decreasing chronic graft-versus-host disease rates in all populations

AbstractSince 2005, there has been a steady decline in chronic graft-versus-host disease (cGVHD) at the Fred Hutchinson Cancer Center. To better understand this phenomenon, we studied the risk of cGVHD requiring systemic immunosuppression (cGVHD-IS) as a function of hematopoietic cell transplantation (HCT) date in 3066 survivors from 2005 through 2019. Cox regression models were fit to assess associations of HCT date (as a continuous linear variable) with cause-specific hazards of cGVHD using unadjusted and adjusted models. Median follow-up for study subjects was 7.0 years (range, 1.0-17.2). Two-year probabilities of cGVHD-IS declined among all survivors from 45% to 52% (2005-2007) to ∼40% (2008-2012) and then further to ∼26% by 2017. A decline was also observed when the analysis was restricted to 502 pediatric survivors, with cGVHD-IS probabilities <10% since 2013. Among 305 adult and pediatric survivors who underwent transplantation for nonmalignant diseases, cGVHD rates showed greater fluctuation but remained <20% after 2016. Each 5-year increase in HCT date was associated with a 27% decrease in the cause-specific hazard of cGVHD (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.68-0.78; P < .0001); the HR was 0.81 (95% CI, 0.75-0.87; P < .0001) even after adjusting for various factors (age, donor/stem-cell source, race, sex, conditioning intensity, GVHD prophylaxis, among others) that could lead to cGVHD reduction. The decline in cGVHD was not fully explained by demographic shifts and greater use of HCT approaches that are generally associated with lower cGVHD rates. This observation underscores that single-cohort cGVHD prevention studies should use contemporaneous and not historical controls for comparison.

Effect of Cancer on Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation - Substudy of the ANAFIE Registry.

Data on outcomes for patients with atrial fibrillation (AF) and active cancer are scarce. The effect of active cancer on thrombosis and bleeding risks in elderly (≥75 years) patients with non-valvular AF (NVAF) enrolled in the All Nippon AF In the Elderly (ANAFIE) Registry were prospectively analyzed. In this subanalysis of the ANAFIE Registry, a prospective, multicenter, observational study conducted in Japan, we compared the incidence rates of clinical outcomes between active cancer and non-cancer groups. Relationships between primary outcomes and anticoagulation status were evaluated. Of the 32,725 patients enrolled in the Registry, 3,569 had active cancer at baseline; 92.0% of active cancer patients received anticoagulants (23.7%, warfarin; 68.2%, direct oral anticoagulants [DOACs]). Two-year probabilities of stroke/systemic embolic events (SEE) were similar in the cancer (3.33%) and non-cancer (3.16%) groups. Patients with cancer had greater incidences of major bleeding (2.86% vs. 2.04%), all-cause death (10.95% vs. 6.77%), and net clinical outcomes (14.63% vs. 10.00%) than those without cancer. In patients without cancer, DOACs were associated with a decreased risk of stroke/SEE, major bleeding, all-cause death, and net clinical outcome compared with warfarin. No between-treatment differences were observed in patients with active cancer. Active cancer had no effect on stroke/SEE incidence in elderly NVAF patients, but those with cancer had higher incidences of major bleeding events and all-cause death than those without cancer.

Adjuvant Radiotherapy After Radical Cystectomy for Patients with High-risk Muscle-invasive Bladder Cancer: Results of a Multicentric Phase II Trial

BackgroundHigh-risk muscle-invasive bladder cancer (MIBC) has a poor prognosis. Old trials showed that external beam radiotherapy (EBRT) after radical cystectomy (RC) decreases the incidence of local recurrences but induces severe toxicity. ObjectiveTo evaluate the toxicity and local control rate after adjuvant EBRT after RC delivered with volumetric arc radiotherapy. Design, setting, and participantsThis is a multicentric phase 2 trial. From August 2014 till October 2020, we treated 72 high-risk MIBC patients with adjuvant EBRT after RC. High-risk MIBC is defined as ≥pT3-MIBC ± lymphovascular invasion, fewer than ten lymph nodes removed, pathological positive lymph nodes, or positive surgical margins. InterventionPatients received 50 Gy in 25 fractions with intensity-modulated radiotherapy to the pelvic lymph nodes ± cystectomy bed. Outcome measurements and statistical analysisThe primary outcome is acute toxicity. We report on local relapse-free rate (LRFR), clinical relapse-free survival (CRFS), overall survival (OS), and bladder cancer–specific survival (BCSS). Results and limitationsThe median follow-up is 18 mo. Forty-two patients (61%) developed acute grade 2 gastrointestinal (GI) toxicity. Four patients (6%) had acute grade 3 GI toxicity. One patient had grade 5 diarrhea and vomiting due to obstruction at 1 mo. Two-year probabilities of developing grade ≥3 and ≥2 GI toxicity were 17% and 76%, respectively. Urinary toxicity, assessed in 17 patients with a neobladder, was acceptable with acute grade 2 and 3 urinary toxicity reported in 53% (N = 9) and 18% (N = 3) of the patients, respectively. The 2-yr LRFR is 83% ± 5% and the 2-yr CRFS rate is 43% with a median CRFS time of 12 mo (95% confidence interval: 3–21 mo). Two-year OS and BCSS are 52% ± 7% and 62% ± 7%, respectively. Shortcomings are the nonrandomized study design and limited follow-up. ConclusionsAdjuvant EBRT after RC can be administered without excessive severe toxicity. Patient summaryIn this report, we looked at the incidence of toxicity and local control after adjuvant external beam radiotherapy (EBRT) following radical cystectomy (RC) in high-risk muscle-invasive bladder cancer patients. We found that adjuvant EBRT was feasible and resulted in good local control. We conclude that these data support further enrollment of patients in ongoing trials to evaluate the place of adjuvant EBRT after RC.

Interferon-α salvage treatment is effective for patients with acute leukemia/myelodysplastic syndrome with unsatisfactory response to minimal residual disease-directed donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation.

The efficacy of salvage interferon-α (IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI) (n = 24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2-3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and > 2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.

Effectiveness of Dolutegravir-Based Regimens as Either First Line or Switch Antiretroviral Therapy: Data from the ICONA Cohort

Background We aimed to estimate the risk of discontinuation (TD) and virological failure (VF) of dolutegravir (DTG)-based regimens. Methods We performed a multicentre, observational study including all antiretroviral therapy (ART)-naA¯ve and virologically suppressed treatment-experienced (TE) patients from the ICONA cohort who started DTG for the first time. We estimated time to DTG-TD and VF using Kaplan-Meier curves. We used Cox regression model to assess predictors of DTG-TD. Findings 1,679 individuals (932 ART-naive, 747 TE) included. The one- and two-year probabilities (95% CI) of DTG-TD were 6⋅7% (4⋅9-8⋅4) and 11⋅5% (8⋅7-14⋅3) for ART-naive and 6⋅6% (4⋅6-8⋅6) and 7⋅6% (5⋅4-9⋅8) for TE subjects. In both ART-naive and TE, DTG-TD was mainly driven by toxicity with an estimated risk (95% CI) of 4⋅0% (2⋅6-5⋅4) and 2⋅5% (1⋅3-3⋅6) by one year and 5⋅6% (3⋅8-7⋅5) and 4⋅0% (2⋅4-5⋅6) by two years, respectively. Neuropsychiatric events were the main reason for DTG-TD in both ART-naive (2⋅1%) and TE (1⋅7%) patients. In ART-naive, a concomitant AIDS diagnosis predicted the risk of DTG-TD for any reason (aRH=3⋅38, p=0⋅001) whereas starting DTG in combination with abacavir (ABC) predicted DTG-TD for toxicity (aRH=3⋅30, p=0⋅009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of DTG-TD for any reason (aHR 2⋅50, p=0⋅037 for ABC-based triple-therapies, aHR 3⋅56, p=0.012 for tenofovir-based) and for toxicity (aHR 5⋅26, p=0⋅030 for ABC-based, aHR 6⋅60,p=0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of VF were 1⋅2% (0⋅3-2⋅0) and 4⋅6% (2⋅7-6⋅5) in the ART naive group and 2⋅2% (1⋅0-3⋅3) and 2⋅9% (1⋅5-4⋅3) in the TE group. Interpretation DTG showed excellent efficacy and tolerability both in ART-naive and TE patients. The low risk of toxicities limiting DTG treatment provide reassuring information in the light of the forthcoming transition to DTG-based first-line therapy in resource-limited countries. Funding: Viiv Healthcare International. Declaration of Interest: AM, ACL, AT, FM and FV have nothing to disclose. SR outside the submitted work reports grants personal fees and non-financial support from ViiV Healthcare,Gilead Sciences and Janssen-Cilag, personal fees and non-financial support from Bristol Myers Squibb and personal fees from Merck Sharp and Dohme. FCS outside the submitted work reports personal fees from Gilead Sciences, Bristol Meyers Squibb, Abbvie, Roche Diagnostic, Janssen-Cilag, Abbott Molecular and ViiV Healthcare, grants and personal fees from Merck Sharp and Dohme and grants from Italian Ministry of Instruction University and Research. AC outside the submitted work reports grants and personal fees from ViiV Healthcare and personal fees from Merck Sharp and Dohme and Janssen-Cilag. ADL outside the submitted work reports grants and personal fees from ViiV 331 Healthcare, Merck Sharp and Dohme and Gilead Sciences and personal fees from Janssen-Cilag and Abbvie. GM outside the submitted work reports personal fees from Gilead Sciences and ViiV Healthcare. AA outside the submitted work reports grants, personal fees and non-financial support from Gilead Sciences, ViiV Healthcare and Bristol Myers Squibb, grants and personal fees from Janssen-Cilag, personal fees from Merck Sharp and Dohme and personal fees and non financial support from Abbvie. AdAM outside the submitted work reports grants and personal fees from Gilead Sciences, ViiV Healthcare and Merck Sharp and Dohme and personal fees from Janssen and Bristol Myers Squibb. Ethical Approval: The Icona Foundation study was approved by the Ethics Committee (IRB) of each participating institution. All of the individuals enrolled provided a written informed consent at the time of the enrolment. All procedures of the study were performed in accordance with the 1964 Helsinki declaration and its later amendments.

Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: Minimum 24‐month follow‐up

Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor for treatment of chronic myeloid leukemia (CML) following resistance/intolerance to prior therapy. Here, we report the data from the 2-year follow-up of a phase 1/2 open-label study evaluating the efficacy and safety of bosutinib as second-line therapy in 288 patients with chronic phase CML resistant (n = 200) or intolerant (n = 88) to imatinib. The cumulative response rates to bosutinib were as follows: 85% achieved/maintained complete hematologic response, 59% achieved/maintained major cytogenetic response (including 48% with complete cytogenetic response), and 35% achieved major molecular response. Responses were durable, with 2-year estimates of retaining response >70%. Two-year probabilities of progression-free survival and overall survival were 81% and 91%, respectively. The most common toxicities were primarily gastrointestinal adverse events (diarrhea [84%], nausea [45%], vomiting [37%]), which were primarily mild to moderate, typically transient, and first occurred early during treatment. Thrombocytopenia was the most common grade 3/4 hematologic laboratory abnormality (24%). Outcomes were generally similar among imatinib-resistant and imatinib-intolerant patients and did not differ with age. The longer-term results of the present analysis confirm that bosutinib is an effective and tolerable second-line therapy for patients with imatinib-resistant or imatinib-intolerant chronic phase CML. http://ClinicalTrials.gov Identifier: NCT00261846. Am. J. Hematol. 89:732–742, 2014. © 2014 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.

Prospective cohort study comparing intravenous busulfan to total body irradiation in hematopoietic cell transplantation

AbstractWe conducted a prospective cohort study testing the noninferiority of survival of ablative intravenous busulfan (IV-BU) vs ablative total body irradiation (TBI)-based regimens in myeloid malignancies. A total of 1483 patients undergoing transplantation for myeloid malignancies (IV-BU, N = 1025; TBI, N = 458) were enrolled. Cohorts were similar with respect to age, gender, race, performance score, disease, and disease stage at transplantation. Most patients had acute myeloid leukemia (68% IV-BU, 78% TBI). Grafts were primarily peripheral blood (77%) from HLA-matched siblings (40%) or well-matched unrelated donors (48%). Two-year probabilities of survival (95% confidence interval [CI]), were 56% (95% CI, 53%-60%) and 48% (95% CI, 43%-54%, P = .019) for IV-BU (relative risk, 0.82; 95% CI, 0.68-0.98, P = .03) and TBI, respectively. Corresponding incidences of transplant-related mortality (TRM) were 18% (95% CI, 16%-21%) and 19% (95% CI, 15%-23%, P = .75) and disease progression were 34% (95% CI, 31%-37%) and 39% (95% CI, 34%-44%, P = .08). The incidence of hepatic veno-occlusive disease (VOD) was 5% for IV-BU and 1% with TBI (P < .001). There were no differences in progression-free survival and graft-versus-host disease. Compared with TBI, IV-BU resulted in superior survival with no increased risk for relapse or TRM. These results support the use of myeloablative IV-BU vs TBI-based conditioning regimens for treatment of myeloid malignancies.

Allogeneic Hematopoietic Stem Cell Transplantation Overcomes the Adverse Prognostic Impact of Minimal Residual Disease in Acute Myeloid Leukemia

Abstract 2027 BACKGROUND:The identification of minimal residual disease (MRD) can predict impending relapse in acute myeloid leukemia (AML) patients. Little data exists evaluating the prognostic impact of MRD, as determined by multiparametric flow cytometry (MFC), at the time of allogeneic (allo-HCT). Although disease outcomes may be worse for MRD positive (MRD+) patients, MRD is often associated with other adverse risk factors leaving it unclear whether MRD is an independent risk factor for relapse or a surrogate marker for underlying poor risk disease features. METHODS:We retrospectively analyzed 97 consecutive AML patients in complete morphological remission (CR) who underwent allo-HCT with a matched related donor (MRD, n=30, 31%), matched unrelated donor (MUD, n=4, 4%) or umbilical cord blood (UCB, n=63, 65%) at the University of Minnesota between January 2005 and June 2009. Presence of MRD at allo-HCT was determined by MFC. Analyses were done separately for myeloablative (MAC) and reduced intensity conditioning (RIC) patients, testing the impact of MRD along with conditioning intensity, age, donor type and disease status on allo-HCT outcomes. RESULTS:Of 97 patients, 41 (42%) had MAC; 57 (58%) had RIC. Sixty-six were in first CR (CR1) with the rest in CR2 or later remission (CR2+). MRD at allo-HCT was detected in 7 patients after MAC (17%) and 7 after RIC (12.5%); and this frequency was similar in patients in CR1 and CR2+ (13% vs. 16%, p=0.7). MRD+ and MRD- patients had similar median age (40 vs. 44 yrs), gender, donor source (MSD or MUD vs. UCB), CMV serostatus and diagnostic cytogenetic risk group. Six of 40 (15%) intermediate and 5 of 39 (13%) high risk cytogenetics patients had MRD+ (p=0.8). Only 3 of 53 patients with a cytogenetic abnormality at diagnosis had it detected prior allo-HCT and 1 of 3 had MRD.The median follow-up of survivors was 25 months. Two-year probabilities for MAC and RIC patients were similar: Overall survival (OS), 48% and 47 % and leukemia free survival (LFS) 43% and 41% respectively. When disease outcomes were analyzed separately by MRD status (table), OS and LFS were markedly worse in MRD+ patients receiving RIC, but this difference was not statistically significant. In multivariate analysis, MRD+ was not an independent prognostic factor for OS and LFS. Although we identified no adverse prognostic factors for MAC patients, patient with RIC in CR2+ had worse OS and LFS vs. CR1 (HR 2.6, p=0.04 and HR 2.7, p=0.04 respectively). CONCLUSION:The negative prognostic impact of MRD was overcome by allo-HCT with MAC, but outcomes with MRD+ were suggestively inferior after RIC. However due to limited sample size, MRD in patients with RIC should be further investigated.2 year outcomesMRD+ (95% CI)MRD− (95% CI)pMACOS43% (10%–73%)49% (32%–65%)0.7LFS43% (10%–73%)44% (27%–60%)0.6RICOS14% (7%–46%)51% (36%–65%)0.1LFS14% (7%–46%)44% (29%–58%)0.1 Disclosures:Weisdorf:Genzyme: Consultancy, Research Funding.

A Pilot Study of Priming With Granulocyte Macrophage Colony-Stimulating Factor Plus All-trans Retinoic Acid Combined With Remission Induction Chemotherapy in Patients With Acute Myeloid Leukemia

Priming with granulocyte macrophage colony-stimulating factor (GM-CSF) plus all-trans retinoic acid (ATRA) during induction chemotherapy may enhance response rates and survival in patients with acute myeloid leukemia (AML) due to the differentiation of human myeloblastic leukemia cells into granulocytes. GM-CSF was administered to patients during induction chemotherapy and ATRA was ingested orally on days 1 to 14. Patients undergoing a regimen with GM-CSF and ATRA were evaluated as compared with a historical control group of subjects. For patients enrolled in this study, the complete remission plus complete remission with incomplete platelet recovery rate was 61.5% as compared with 41.4% for the historical control group of subjects. The relapse rate was 38.5% and 44.8% for the study and control group of subjects, respectively. Two-year probabilities were 45.5% (study group) and 47.4% (control group) for disease-free survival and 38.5% (study group) and 36.2% (control group) for overall survival. The most frequent side effects included fever, headache, and skin lesions with pruritus and dyspnea with pulmonary congestion, similar to ATRA syndrome. Priming with GM-CSF plus ATRA during anthracycline-based chemotherapy is feasible in terms of response rate, but the toxicity of the regimen is significant.

Phase II Trial of a Chemotherapy-Only Regimen of Busulfan, Melphalan, Fludarabine and R-ATG Followed by Allogeneic T-Cell Depleted (TCD) Hematopoietic Stem Cell Transplants (HSCT) for the Treatment of Myeloid Malignancies.

In this trial, we wished to test whether a chemotherapeutic regimen combining myeloablation with busulfan (Bu) and melphalan (Mel) with fludarabine (Flu) and ATG could be used to secure consistent engraftment of T-cell depleted transplants thereby reducing GvHD and regimen-related toxicity without increasing risk of relapse in patients with advanced myeloid malignancies. Between 08/01 and 06/07, sixty two patients with a diagnosis of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) were enrolled on this trial, including 33 males and 29 females of a median age of 54.5 years (range 0.6–71.3 years). Eleven patients had primary AML in CR1 (N=4) or ≥ CR2 (N=7). Thirty two pts had primary (1°) MDS and 19 pts treatment related (2°) MDS/AML. Forty five of the 51 pts with 1° or 2° MDS had ≥ RAEB status at diagnosis and required chemotherapy prior to transplant. The status of MDS pts at the time of SCT included: CR1 (N=14), CR2 (N=3), primary RA (N=6), second RA (N=21), > RA (N=7). Thirteen pts received allografts from HLA-matched related donors, 4 pts from HLA-mismatched related donors, 22 pts from HLA-matched unrelated donors, and 23 pts from HLA-mismatched unrelated donors. Cytoreduction consisted of BU (0.8–1 mg/Kg/dose × 10 doses), MEL (70 mg/Kg/day × 2) and FLU (25 mg/m2/day × 5). Graft rejection prophylaxis included pre-transplant rabbit ATG (Thymoglobulin) (2.5 mg/Kg/day × 2) and no post transplant immunosuppression was administered. Fifty nine pts received G-CSF mobilized peripheral blood stem cell transplants (PBSCT) that were T-cell depleted by positive CD34 selection and sheep-RBC rosetting while three pts received soybean agglutinin E-rosette depleted marrow grafts. For the PBSCT grafts, the median CD34+ cell dose/Kg was 5.0 × 106 (range: 1.3–28.8 × 106) and the median CD3+ cell dose/Kg was 1.1 × 103 (range 0–12 × 103). Median follow-up was 16 months (range 0.7–68.7 mo). Engraftment occurred in 59 of 61 evaluable pts, but two recipients of unrelated donor grafts suffered a graft failure. Acute grade 2–4 GvHD occurred in 7 pts, and chronic GvHD in three of 40 evaluable pts. Twenty two pts died of infection (n=7), organ toxicity (n=6), GvHD (n=3), graft failure (n=1) or relapse (n=5). The two-year probabilities of overall survival (OS) and disease-free survival (DFS) for the entire patient cohort were 62% and 54% respectively with a two-year probability of relapse of 16.2%.The two-year DFS for recipients of HLA-matched related and unrelated grafts was 54% and 57% for recipients of HLA-disparate unrelated grafts. Two-year DFS was 58% for pts with primary AML, 57% for pts with primary MDS and 51% for pts with secondary MDS/AML. Two-year DFS was 60.6% for pts ≤ 50 years and 49.7% for pts > 50 years. In summary, cytoreduction with Bu Mel and Flu and rabbit ATG has secured consistent engraftment of T-cell depleted transplants for both HLA-matched or disparate, related and unrelated donors. The incidence of acute or chronic GvHD and disease relapse were low, with favorable outcomes in this cohort of older patients with high risk myeloid malignancies.

Bone Marrow Transplantation for Fanconi Anemia

Abstract Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.

Bone marrow transplantation for Fanconi anemia

Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.