Unrelated cord blood compared with haploidentical grafts in patients with hematological malignancies.

BACKGROUND: Alternative donors, such as unrelated umbilical cord blood (UCB) and related haploidentical (haplo) donors, are more and more frequently searched for and used for patients who are candidates for allogeneic hematopoietic stem cell transplantation but are without a suitable related or unrelated donor. The aim of the current retrospective study was to compare the outcome of patients after haplo and UCB grafts prepared using a nonmyeloablative conditioning regimen. METHODS: A total of 150 adult patients with high-risk hematologic diseases who underwent allogeneic hematopoietic stem cell transplantation from alternative donors at 2 centers (Paoli-Calmettes Institute [Marseille, France] and Humanitas Cancer Center [Milan, Italy]) were analyzed. Sixty-nine patients had haplo donors and 81 patients had UCB donors. RESULTS: The cumulative incidence of nonrecurrence mortality at 1 year was 23% in the UCB group versus 17% in the haplo group (P = .39). The incidence of grade 2 to 4 acute graft-versus-host disease and extensive chronic graft-versus-host disease in the UCB group versus the haplo group was 52% versus 29% (P = .05) and 12% versus 6% (P<.0001), respectively. The overall survival rate at 2 years was 45% in the UCB group (95% confidence interval [95% CI], 34%-56%) versus 69% in the haplo group (95% CI, 58%-80%) (P = .10). The progression-free survival rate at 2 years was 36% in the UCB group (95% CI, 25%-47%) versus 65% in the haplo group (95% CI, 53%-77%) (P = .01). CONCLUSIONS: The results of the current study suggest that for patients with high-risk hematological diseases without a related or unrelated donor, haploidentical transplants are a promising alternative option that deserves further investigation.

Allogeneic Hematopoietic Cell Transplantation with Non-Myeloablative Conditioning and Post-Transplant Cyclophosphamide Prophylaxis in Patients with Reduced Systolic Function.

Post-transplantation cyclophosphamide (PTCy) has become standard of care for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic cell transplantation (alloHCT), allowing for expanded donor options. However, there is scant literature examining outcomes of patients with reduced systolic function receiving PTCy. The present study aimed to describe our experience in performing alloHCT in patients with reduced systolic function, including their nonrelapse mortality (NRM), overall survival (OS), and cumulative incidence of early cardiac events (ECEs). We performed a retrospective descriptive analysis using the Johns Hopkins Hematologic Malignancy database. From 2017 through 2021, 1118 consecutive patients underwent alloHCT with nonmyeloablative (NMA) conditioning and PTCy. Forty-three of those patients had a pretransplantation left ventricular ejection fraction (LVEF) ≤45% measured by transthoracic echocardiography. Patients whose LVEF improved on treatment prior to transplantation were also included. These 2 cohorts were stratified into 2 groups-heart failure with reduced ejection fraction (HFrEF) and heart failure with recovered ejection fraction (HFrecEF)-and subgroup analyses compared NRM, OS, and cumulative incidence of ECEs, including arrhythmia, coronary artery disease, reduction in LVEF, and pericardial effusion, within 100 days post-transplantation. The median LVEF was 40% to 45% (range, 30% to 45%) for the 31 patients undergoing transplantation with HFrEF and 35% to 40% (range, 20% to 45%) for the 12 patients with HFrecEF. The NRM for all 43 patients was 16% (95% confidence interval [CI], 5% to 27%) at 100 days and 23% (95% CI, 11% to 36%) at 2 years. The NRM was 23% (95% CI, 8% to 38%) at 100 days and 26% (95% CI, 10% to 42%) at 2 years for the HFrEF cohort and 0 at 100 days and 18% (95% CI, 0 to 41%) at 2 years for the HFrecEf cohort. The OS at 3 years was 41% (95% CI, 26% to 62%), 40% (95% CI, 25% to 65%) and 38% (95% CI, 14% to 100%) in the combined, HFrEF, and HFrecEF cohorts, respectively. The cumulative incidence of any ECE was 37.2% (95% CI, 22% to 51.9%), including 39% of HFrEF subjects and 33% of HFrecEF subjects. Grade ≥3 toxicities were seen in 56% of patients. Reduced ejection fraction was the most common ECE. One death was attributable to a cardiac etiology. Cardiac toxicities seemed to be more frequent and severe in patients with a history of systolic dysfunction, but this did not lead to worse survival outcomes. This study adds to and extends the existing literature supporting the use of NMA conditioning and PTCy in patients with systolic dysfunction.

Comparing high and low total body irradiation dose rates for minimum-intensity conditioning of dogs for dog leukocyte antigen-identical bone marrow grafts.

We tested the hypothesis that total body irradiation (TBI) given at a high dose rate would be more immunosuppressive and lead to a higher incidence of stable hematopoietic cell engraftment after suboptimal levels of conditioning irradiation compared with TBI at a low dose rate. We assessed the engraftment success of dog leukocyte antigen-identical bone marrow transplantation in recipients of 100, 150, and 200 cGy TBI administered at a rate of 7 or 70 cGy/min. Dogs received donor marrow on the same day as TBI and were subsequently treated with postgraft immunosuppression consisting of mycophenolate mofetil (for 28 days) and cyclosporine (for 37 days). Donor chimerism was monitored until the end of study and was characterized by either graft rejection or stable engraftment. Increasing the radiation dose rate from the traditional 7 cGy/min to 70 cGy/min did not lead to increased engraftment success at any of the irradiation doses tested. The dose rate of 70 cGy/minute was no more hematotoxic than the rate of 7 cGy/minute. TBI delivered at a high dose rate was well tolerated but was not associated with a better rate of allogeneic hematopoietic cell engraftment compared with TBI delivered at a lower dose rate.

Engraftment of Double Cord Blood Transplantation after Nonmyeloablative Conditioning with Escalated Total Body Irradiation Dosing to Facilitate Engraftment in Immunocompetent Patients.

To improve accrual to a randomized clinical trial of double unrelated cord blood (dUCB) versus HLA-haploidentical bone marrow (haplo-BM) transplantation, patients with less previous therapy and potentially greater immunocompetence were enrolled. To reduce the risk of graft rejection, patients randomized to receive dUCB received a higher dose of total body irradiation (TBI) (300 cGy versus 200 cGy). In this study, we investigated whether the inclusion of recipients of 300 cGy TBI influenced the trial outcomes. This was a secondary analysis of dUCB recipients, 161 who received TBI 200 cGy and 18 who received TBI 300 cGy. Fine and Gray regression was used to evaluate the effect of TBI dose on relapse and nonrelapse mortality (NRM). Cox regression was used for evaluation of neutrophil engraftment and overall survival. Patient characteristics were similar in the 2 TBI dose subgroups. The probability of neutrophil engraftment was 100% for patients who received TBI 300 cGy versus 91% (95% confidence interval, 86% to 95%) for those who received TBI 200 cGy (P = .64), which was similar after regression analysis adjusting for age, total infused nucleated cell dose, HLA matching to the patient, and comorbidity score. We also investigated whether the lower survival probability and higher cumulative incidence of NRM observed in the dUCB arm of BMT CTN 1101 could be influenced by the TBI 300 cGy patient subset. There was no significant difference in the 1-year incidences of NRM and relapse or in 1-year survival, even after adjustment in multivariate analysis. Patients in BMT CTN 1101 who received TBI 300 cGy and 200 cGy had similar engraftment and early mortality. We conclude that inclusion of a modified regimen for dUCB transplantation had no demonstrable influence on this large randomized trial.