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We conducted a phase I study of brentuximab vedotin (BV), an antibody-drug conjugate targeting CD30, for the treatment of steroid-refractory chronic graft-versus-host disease (cGVHD). A modified 3 + 3 study design was used with the primary endpoint to determine the maximum tolerated dose of BV in this population. Escalating doses of BV were planned, starting with .6 mg/kg every 3 weeks (dose level 0) and increasing by .3 mg/kg per dose level. BV was administered in 21-day cycles for up to 16 cycles of therapy. Nineteen patients were enrolled on the study, with 2 withdrawing consent before dosing. The median number of cycles of therapy was 4 (range, 1 to 16). Reasons for stopping therapy prematurely included toxicities (n = 9), patient decision (n = 3), lack of response (n = 2), and death (n = 1). There were 2 dose-limiting toxicities observed: posterior reversible encephalopathy syndrome (cohort 4, grade 3) and sepsis (cohort 4, grade 4). The maximum tolerated dose was not reached because the trial was prematurely closed due to toxicity. Seven patients (41%) developed grade 3 or 4 adverse events that were attributed to therapy, including 4 patients who developed moderate or severe peripheral neuropathy that led to cessation of treatment in each case. According to National Institutes of Health cGVHD response criteria, 8 patients (47%) experienced a partial response, whereas 9 patients (53%) had a lack of response. There were no complete responses observed. Eleven patients (65%) were able to decrease their systemic corticosteroid dose by ≥50% by 6 months after initiation of BV, including 3 patients who were able to stop corticosteroids completely. The median soluble CD30 level before therapy was 61.5 ng/mL (range, 7.8 to 474.9); however, we did not observe any association between soluble CD30 level and cGVHD severity at enrollment or clinical responses to BV. In conclusion, BV may have activity in treatment of steroid-refractory cGVHD, yet its use is limited by treatment-emergent toxicities, including peripheral neuropathy. Continued efforts to investigate targeted approaches to cGVHD that do not cause broad immunosuppression are needed., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The impact of advances in supportive care and hematopoietic stem cell transplantation (HSCT) practices on the outcomes of patients who develop grade III or IV acute graft-versus-host disease (GVHD) is unknown. We performed a retrospective analysis of 427 patients with overall grade III or IV acute GVHD treated at 2 partner institutions between 1997 and 2012. We compared treatment-related mortality (TRM) and overall survival (OS) in 2 cohorts based on the year of transplantation, 1997 to 2006 (n = 222) and 2007 to 2012 (n = 205), using multivariate analysis, adjusting for significant patient-, disease-, and transplantation-related factors. Recipient age, reduced-intensity conditioning, unrelated donor, and peripheral blood stem cell grafts in the patients with grade III or IV acute GVHD increased over time. In the unadjusted analysis, 12-month OS increased over time (30% in 1997 to 2006 versus 42% in 2007 to 2012; P = .003) reflecting a decrease in TRM (58% in 1997 to 2006 versus 38% in 2007 to 2012; P = .0002), and an increase in PFS (29% in 1997 to 2006 versus 43% in 2007 to 2012; P = .002). On multivariate analysis, the period of transplantation remained a significant predictor for OS (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.54 to 0.94; P = .02), progression-free survival (PFS) (HR, 0.70; 95% CI, 0.52 to 0.94; P = .02), and TRM (HR, 0.57; 95% CI, 0.39 to 0.82; P = .002). In subgroup analysis, these differences were observed mainly in patients with grade IV acute GVHD. The outcomes of patients who develop overall grade III or IV acute GVHD after allogeneic HSCT has improved over time, with lower TRM and improved OS. This improvement in outcomes was seen primarily in patients with grade IV acute GVHD., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Clofarabine has potent antileukemia activity and its inclusion in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia could potentially improve outcomes. We conducted a phase II study of busulfan (.8 mg/kg i.v. twice daily on days -5, -4, -3, and -2) with clofarabine (40 mg/m(2) i.v. daily on days -5, -4, -3, and -2) conditioning before allogeneic 8/8 HLA-matched related or unrelated HSCT. The primary endpoint was donor neutrophil engraftment by day +40. Secondary endpoints included nonrelapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), progression-free survival (PFS), and overall survival (OS). Thirty-four patients (acute myeloid leukemia [AML], n = 25; myelodysplastic syndromes, n = 5; and acute lymphoid leukemia, n = 4) were enrolled. Day 40+ engraftment with donor chimerism was achieved in 33 of 34 patients with 1 patient dying before count recovery. Day 100 and 1-year NRM were 5.9% (95% confidence interval [CI], 1.0 to 17.4) and 24% (95% CI, 11 to 39), respectively. The 2-year relapse rate was 26% (95% CI, 13 to 42). Cumulative incidences of acute and chronic GVHD were 21% and 44%, respectively. The 2-year PFS was 50% (95% CI, 32 to 65) and OS was 56% (95% CI, 38 to 71). For patients with AML in first complete remission, 2-year PFS and OS were both 82% (95% CI, 55 to 94). RIC with busulfan and clofarabine leads to successful engraftment with acceptable rates of NRM and GVHD., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation is associated with a high relapse rate for patients with acute myeloid leukemia (AML) even after allogeneic hematopoietic stem cell transplantation (HSCT). Sorafenib is a tyrosine kinase inhibitor, which inhibits the FLT3 tyrosine kinase and has shown encouraging activity in FLT3-ITD AML. We conducted a phase I trial of maintenance sorafenib after HSCT in patients with FLT3-ITD AML (ClinicalTrials.govNCT01398501). Patients received a variety of conditioning regimens and graft sources. A dose escalation 3 + 3 cohort design was used to define the maximum tolerated dose (MTD), with an additional 10 patients treated at the MTD. Sorafenib was initiated between days 45 and 120 after HSCT and continued for 12 28-day cycles. Twenty-two patients were enrolled (status at HSCT: first complete remission [CR1], n = 16; second complete remission [CR2], n = 3; refractory, n = 3). The MTD was established at 400 mg twice daily with 1 dose-limiting toxicity (DLT) observed (pericardial effusion). Two patients died of transplantation-related causes, both unrelated to sorafenib. Two patients stopped sorafenib after relapse and 5 stopped because of attributable toxicities after the DLT period. Median follow-up for surviving patients is 16.7 months after HSCT (range, 8.1 to 35.0). There was 1 case of grade II acute graft-versus-host disease (GVHD) after starting sorafenib and the 12-month cumulative incidence of chronic GVHD was 38% (90% confidence interval [CI], 21% to 56%). For all patients, 1-year progression-free survival (PFS) was 85% (90% CI, 66% to 94%) and 1-year overall survival (OS) was 95% (90% CI, 79% to 99%) after HSCT. For patients in CR1/CR2 before HSCT (n = 19), 1-year PFS was 95% (90% CI, 76% to 99%) and 1-year OS was 100%, with only 1 patient who relapsed. Sorafenib is safe after HSCT for FLT3-ITD AML and merits further investigation for the prevention of relapse., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Graft-versus-host disease (GVHD) is a donor T cell driven response against host tissue that can complicate allogeneic hematopoietic stem cell transplantation (HSCT). During acute GVHD, endogenous adjuvants such as uric acid are released by damaged host tissue, activating alloreactive donor T cells. A phase I study was conducted at the Massachusetts General Hospital between 2007 and 2010 to test the hypothesis that reduction of uric acid levels during allogeneic HSCT can modulate the development of acute GVHD. Twenty-one patients with hematologic malignancies in complete remission undergoing myeloablative peripheral blood HSCT received recombinant urate oxidase at .20 mg/kg for 5 consecutive days during conditioning. Results were compared with all patients who underwent allogeneic HSCT at our institution during the same time period who met the same inclusion and exclusion criteria but were not enrolled in the study. The only major adverse event was a case of hemolytic anemia in a patient who had glucose-6-phosphate dehydrogenase deficiency. Primary outcome was the cumulative incidence of grades II to IV acute GVHD, which was significantly decreased in the treatment group in the intention-to-treat analysis (57% [12/21] versus 24% [5/21], P = .036) and in the per-protocol analysis (P = .017). Patients who developed acute GVHD had a higher level of serum uric acid during the pretransplantation period compared with those who did not (P < .001). There was no difference in disease-free or overall survival. Our study suggests that urate oxidase can be safely administered during myeloablative conditioning and may reduce the incidence of acute GVHD., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Allogeneic hematopoietic stem cell transplantation (HSCT) can achieve durable remissions in a number of patients with advanced hematologic malignancies. Little is known about the safety of HSCT in patients age 70 or older. Consecutive patients (n = 54) age 70 or older underwent HSCT between 2007 and 2012. Diseases included acute myelogenous leukemia (n = 25), myelodysplastic syndrome (n = 12), chronic lymphocytic leukemia (n = 5), non-Hodgkin lymphoma (n = 4), acute lymphoblastic leukemia (n = 3), myeloproliferative neoplasm (n = 4), and chronic myelogenous leukemia (n = 1). Median follow-up for survivors was 21 months. All patients received reduced-intensity conditioning regimens, primarily busulfan/fludarabine. All patients received unmanipulated peripheral blood stem cell grafts: 44 from 8/8 matched unrelated donors, 8 from matched related donors, and 2 from 7/8 matched unrelated donors. Graft-versus-host disease (GVHD) prophylaxis was calcineurin inhibitor-based in all patients. The median age at transplantation was 71 years (range, 70 to 76); the median HCT comorbidity index score was 1 (range, 0 to 5). Two patients died before hematopoietic recovery (1 with graft failure and 1 with disease progression), and 1 patient relapsed before hematopoietic recovery; otherwise, all engrafted with median donor chimerism of 94% at 1 month. Cumulative incidence of grades II to IV acute GVHD was 13% and of grades III to IV acute GVHD, 9.3%. At 2 years, the cumulative incidence of chronic GVHD was 36%, progression-free survival was 39%, overall survival was 39%, and relapse was 56%. Nonrelapse mortality was 3.7% at day +100 and 5.6% at 2 years. We conclude that allogeneic HSCT is a safe and effective option for carefully selected patients age 70 or older., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Invasive fungal disease (IFD) is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HCT). We performed a retrospective review of 271 adults with a hematologic malignancy undergoing allogeneic HCT to determine the incidence of and risk factors for IFD and to examine the impact of IFD on nonrelapse mortality and overall survival. We defined IFD using standard criteria and selected proven and probable cases for analysis. Diagnoses in the study group included acute leukemia (42%), non-Hodgkin lymphoma (24%), myelodysplastic syndrome (15%), chronic lymphocytic leukemia (5%), and other hematologic disorders (14%). Conditioning included reduced-intensity (64%) and myeloablative (36%) regimens. Donor sources were HLA-matched sibling (60%), matched unrelated (20%), haploidentical (12%), and cord blood (8%). A total of 51 episodes of IFD were observed in 42 subjects (15%). Aspergillus spp (47%) was the most frequent causative organism, followed by Candida spp (43%). The majority of IFD cases (67%) were reported after day +100 post-HCT. In multivariate analysis, haploidentical donor transplantation (hazard ratio [HR], 3.82; 95% confidence interval [CI], 1.49-9.77; P = .005) and grade II-IV acute graft-versus-host disease (HR, 2.55; 95% CI, 1.07-6.10; P = .03) were risk factors for the development of IFD. Conversely, higher infused CD34(+) cell dose was associated with a lower risk of IFD (HR, 0.80; 95% CI, 0.68-0.94; P = .006, per 1 × 10(6) cells/kg increase in CD34(+) cell infusion). IFD-related mortality was 33.3%. Nonrelapse mortality was significantly higher in patients who developed IFD compared with those without IFD (P < .001, log-rank test). Patients with IFD had lower overall survival (5.8 months versus 76.1 months; P < .001, log-rank test). Further studies exploring strategies to increase the infused cell dose and determine adequate prophylaxis, especially against aspergillus, beyond day +100 are needed., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Comparisons of myeloablative conditioning versus reduced-intensity conditioning (RIC) have demonstrated a tradeoff between relapse and toxicity. Dose intensity across RIC regimens vary and may affect treatment outcomes. In this retrospective analysis, we investigated the effect of i.v. busulfan dosing (total dose 3.2 mg/kg versus 6.4 mg/kg) in RIC regimens that combined fludarabine and busulfan on outcomes in patients who were undergoing hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). A total of 217 consecutive patients with MDS or AML underwent first busulfan and fludarabine RIC peripheral blood stem cell transplantation from well-matched related or unrelated donors at our institutions between 2004 and 2009. Of the 217 patients, 135 patients received Bu1 (3.2 mg/kg of busulfan) and 82 patients received Bu2 (6.4 mg/kg of busulfan), both with daily fludarabine (30 mg/m(2)/day for 4 days). The choice of RIC regimen was based on temporal institutional standard, enrollment on protocols, and physician choice. Patients had similar characteristics with a few notable differences: Patients who received Bu1 were younger (median age 61 versus 64 years, P < . 001), received more single-antigen mismatched unrelated grafts (14.1% versus 1.2%, P < . 001), received more sirolimus-based graft-versus-host disease (GVHD) prophylaxis regimens (63% versus 45%, P < .0001), received less antithymocyte globulin for GVHD prophylaxis (0% versus 22%, P < .001), and had less enrollment on a clinical trial that used prophylactic rituximab for the prevention of chronic GVHD (2.2% versus 11.0%, P = .011). Clinical disease status was similar between the groups. Median follow-up for survivors was 4.4 years for Bu1 and 3.2 years for Bu2. Because of the differences in characteristics, the 2 groups were compared with the adjustment of a propensity score that predicted Bu2 to account for measured differences. The day +200 cumulative incidence rates of grades II to IV acute GVHD (Bu1, 17%, versus Bu2, 8.5%; hazard ratio [HR], .56; 95% confidence interval [CI], .22 to 1.41; P = .22) or grades III to IV acute GVHD (Bu1, 6.7%, versus Bu2, 4.9%) were not different. The 2-year cumulative incidence of chronic GVHD was not significantly different between Bu1 and Bu2 (41.5% versus 28%, respectively; HR, .70; CI, .42 to 1.17; P = .09). Two-year nonrelapse mortality rates were similar for Bu1 and Bu2 (8.9% versus 9.8%, respectively; HR, .80; CI, .29 to 2.21; P = .67). Two-year progression-free survival and overall survival were also similar between Bu1 and Bu2 (progression-free survival: 40.6% versus 39.3%, respectively; HR, .82; CI, .57 to 1.30; P = .33; and overall survival: 47.4% versus 48.8%, respectively; HR, .96; CI, .64 to 1.44; P = .85). Subset analysis defined by clinical disease and cytogenetic risk with the propensity risk score applied suggest that in patients with high clinical disease risk and nonadverse cytogenetics, the higher dose busulfan RIC regimen may be of marginal benefit (2-year progression-free survival: HR, .54; CI, .29 to 1.03; P = .062). For the majority of patients with MDS or AML undergoing busulfan and fludarabine RIC peripheral blood stem cell transplantation, however, the dose of busulfan (3.2 mg/kg versus 6.4 mg/kg) is not associated with significant differences in overall outcomes., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Transplantation of 1 or 2 umbilical cord blood products is a useful alternative stem cell source. However, the limited number of stem cells in each infusion results in slow engraftment. In mouse models, administration of parathyroid hormone (PTH) is an effective way to enhance the ability of limited numbers of hematopoietic stem cells to support hematopoiesis. In this study, patients received either a myeloablative or a reduced-intensity double umbilical cord blood transplantation, followed by PTH at 100 μg/day for 28 days. Thirteen patients (median age, 42 years) were enrolled. All patients engrafted; the median time to neutrophil and platelet engraftment of >20 × 10(9) cells/L was 30 days and 61 days, respectively. The incidence of grade II-IV acute GVHD was 38.5% at day 100. Four deaths occurred before day 100, prompting early study closure. No patient who received a myeloablative regimen relapsed. Overall survival at 6 months after transplantation was 62%, and disease-free survival at 2 years was 39%. At the dose and schedule studied, there was no evidence that PTH influenced blood count recovery., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Double umbilical cord blood transplantation (UCBT) with a reduced-intensity conditioning regimen is an effective strategy for adult patients without a matched donor. The risk of second malignancies in these patients has not yet been established, however. In the present study, 98 adults with a hematologic malignancy underwent double UCBT. Seventy patients received a reduced-intensity conditioning regimen of fludarabine 30 mg/m(2)/day for 6 days, melphalan 100 mg/m(2)/day for 1 day, and rabbit antithymocyte globulin 1.5 mg/kg/day for 4 days, and 28 patients received a myeloablative total body radiation-containing conditioning regimen. Sixty-three patients received sirolimus-based graft-versus-host disease (GVHD) prophylaxis, and 35 patients received non-sirolimus-based GVHD prophylaxis. The median patient age was 48 years (range, 19-67 years). Eighteen patients developed a second malignancy at a median of 134 days after transplantation. Sixteen patients had lymphoma, and 2 patients had myelodysplasic syndrome/myeloproliferative disorder (MDS/MPD). Sixteen of these second malignancies (both cases of MDS/MPD and 14 of the lymphomas) were donor-derived; the origins of the others were not determined. GVHD prophylaxis, HLA matching, primary disease, age, total nucleated cell dose, and CD34(+) cell dose were not associated with a higher rate of second malignancy. Second myelogenous malignancies of donor origin occur after double UCBT, suggesting that a search for donor origin should be performed in all patients with suspected relapse.

High-dose chemotherapy with autologous stem cell transplantation (ASCT) has been established as a standard form of therapy for patients with non-Hodgkin lymphoma (NHL). While many high-dose chemotherapy combinations are used, no single regimen has proved superior over another. Here, we report our single center's experience in patients with NHL undergoing ASCT with the combination of busulfan and cyclophosphamide (Bu/Cy). This study is a retrospective analysis of 78 consecutive patients with NHL who underwent ASCT with Bu/Cy at Massachusetts General Hospital Cancer Center. Data were collected through review of electronic medical records. A total of 78 patients with NHL underwent ASCT with Bu/Cy preparative therapy between 1996 and 2006. Median follow-up for survivors was 5.0 years (range, 6 months to 12 years). Significant transplantation-associated complications included 9 documented bacterial infections, 4 cases of engraftment syndrome, 3 cases of hepatic veno-occlusive disease (VOD), 6 cases of cardiac complications, and 2 cases of pulmonary fibrosis. The 100-day treatment-related mortality (TRM) was 1%. At 3 years, progression-free survival (PFS) was 48% (95% confidence interval [CI]=37% to 59%) and overall survival (OS) was 65% (95% CI=53% to 74%). Our data indicate that in patients with NHL undergoing ASCT, Bu/Cy has efficacy and toxicity comparable to that of other reported regimens.

Autologous stem cell transplantation is a curative procedure for many patients with lymphomas, and has been shown to improve survival in patients with multiple myeloma. Approximately 20% of patients are unable to mobilize sufficient hematopoietic stem cells to proceed safely to autologous stem cell transplantation. Parathyroid hormone (PTH) affects osteoblasts and the stem cell niche, and has been shown to improve survival when given posttransplant in a mouse competitive transplant model. In this Phase I study, 20 subjects who had 1 or 2 unsuccessful stem cell mobilization attempts, received PTH in escalating doses of 40 microg, 60 microg, 80 microg, and 100 microg for 14 days. On days 10-14 of treatment, subjects received filgrastim 10 microg/kg. The PTH was tolerated well and there was no dose-limiting toxicity. Forty-seven percent of subjects who had failed 1 prior mobilization attempt met the mobilization criteria of >5 CD 34(+) cells/microL in the peripheral blood. Forty percent of subjects who failed to reach adequate CD34(+) cell counts in 2 prior mobilization attempts met the mobilization criteria. PTH was well tolerated at doses up to 100 microg in human cancer patients. The efficacy of PTH for mobilization of hematopoietic stem cells will need to be tested in a larger Phase II study.

Umbilical cord blood (UBC) stem cells are a useful stem cell source for patients without matched related or unrelated donors. Adult transplantation with single UBC units is associated with high transplantation-related mortality (TRM). In most cases, mortality is due to infection related to slow engraftment and immunoincompetence. In this study, we used a reduced-intensity conditioning regimen of fludarabine, melphalan, and antithymocyte globulin followed by 2 partially matched UBC units. The UBC units were a 4/6 HLA match or better with each other and with the patient and achieved a minimum precryopreservation cell dose of 3.7 x 10(7) nucleated cells/kg. A total of 21 patients (median age, 49 years) were treated. The median time to an absolute neutrophil count > 0.5 x 10(9)/L was 20 days, and the median time to an unsupported platelet count > 20 x 10(9)/L was 41 days. Two patients experienced primary graft failure and underwent a second UBC transplantation. One patient had a late graft failure. Acute graft-versus-host disease (GVHD) grade II-IV occurred in 40% of patients. The 100-day TRM was 14%, and the 1-year disease-free survival was 67%. Mixed chimerism was associated with a higher risk of chronic GVHD. Our findings indicate that adult patients can tolerate double UBC transplantation well and achieve sustained antitumor responses using this reduced-intensity conditioning regimen.

In an attempt to capture graft-versus-tumor effects without graft-versus-host disease (GVHD), the authors initiated a trial of nonmyeloablative allogeneic bone marrow transplantation (BMT) in patients with advanced hematologic malignancies, with the majority of patients having chemotherapy-refractory disease. Forty-two patients received an HLA-matched related donor BMT after a cyclophosphamide and antithymocyte globulin-based conditioning that also included thymic irradiation for patients who had not received prior mediastinal radiotherapy. Prophylactic donor leukocyte infusion (pDLI) at a dose of 1 x 10(7) CD3(+) cells per kilogram were given beginning 5 weeks post-BMT to 16 patients with mixed chimerism (MC) but without GVHD, whereas 26 patients did not receive pDLI, either because of GVHD or early relapse. Twelve of 16 patients (75%) receiving pDLI had T cell chimerism at the time of pDLI >/=40%. These patients, by day 100 post-BMT, either converted to full donor chimerism (FDC) (n = 10) or had an increase in or stable donor chimerism (n = 2) after pDLI. Four of 4 patients whose T cell chimerism was /=grade II acute GVHD, including 12 after BMT and 7 after pDLI. Approximately one third of patients, after having initial MC, eventually lost their donor graft. The authors conclude that (1) pDLI has the potential to convert MC to FDC; (2) sustained remissions can be achieved in patients with chemorefractory hematologic malignancies who receive a pDLI, albeit with a significant risk of acute GVHD; and (3) the degree of donor T cell chimerism at the time of pDLI is predictive of the fate of MC, ie, donor T cell chimerism >/=40% or

The use of myeloablative preparative therapy and allogeneic stem cell transplantation (alloSCT) as salvage therapy for adult patients with relapsed hematologic malignancy after autologous stem cell transplantation (autoSCT) is generally unsuccessful due to very high treatment-related mortality rates. We evaluated the outcome of HLA-matched related donor alloSCT following nonmyeloablative preparative therapy in 13 patients (median age, 38 years) with relapsed hematologic malignancies (Hodgkin's disease, n = 4; Hodgkin's disease and advanced myelodysplastic syndrome, n = 1; non-Hodgkin's lymphoma, n = 6; multiple myeloma, n = 2) after initial autoSCT. Median time from autoSCT to alloSCT was 12 months (range, 3-24 months); 6 patients had chemotherapy-refractory disease following autoSCT, 6 were in untreated relapse, and 1 had a partial response from salvage chemotherapy. Preparative therapy consisted of cyclophosphamide, 150-200 mg/kg; peritransplantation anti-thymocyte globulin; thymic irradiation (in patients who had not received previous mediastinal irradiation); and a very short course of cyclosporine as GVHD prophylaxis. All patients achieved initial mixed chimerism as defined by greater than 1% donor peripheral white blood cells. Seven patients, who had no evidence of GVHD, received prophylactic DLI beginning 5 to 6 weeks after transplantation for conversion of mixed chimerism to full donor hematopoiesis and to optimize a graft-versus-tumor effect. Six patients showed conversion to full donor chimerism and 1 lost the graft. Grade II or greater acute GVHD occurred in 9 patients. Seven patients achieved a complete response; 6 had no response. The median survival time of the 13 patients is currently 10 months (range, 3-39 months), with an overall survival probability at 2 years of 45% (95% confidence interval [CI], 19%-73%) and a disease-free survival probability at 2 years of 37.5% (95% CI, 12%-65%). Thus, this novel nonmyeloablative alloSCT strategy followed by prophylactic DLI was well tolerated and can result in durable disease-free survival among patients with advanced hematologic malignancies after a failed autoSCT. Further follow-up and evaluation of additional patients are required to conclusively establish the role of this strategy in the treatment of hematologic malignancies after an autologous transplantation.