Pretransplant myeloid and immune suppression, reduced toxicity conditioning with posttransplant cyclophosphamide: Initial outcomes of novel approach for matched unrelated donor hematopoietic stem cell transplant for hemoglobinopathies.

Hematopoietic stem cell transplant (HSCT) is currently the only curative option for thalassemia major (TM) and sickle cell disease (SCD). We report our experience of using pretransplant immune suppression (PTIS), augmented Johns Hopkins conditioning, and posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GvHD) prophylaxis for matched unrelated donor (MUD) transplant in TM/SCD. At a median follow-up of 307.5 days (range 251-395), all patients (three TM, one SCD) are alive and disease free. MUD HSCT with PTIS, augmented Johns Hopkins conditioning, and PTCy as GvHD prophylaxis is a promising way of treating patients with hemoglobinopathies with low regimen-related toxicity (RRT), no risk of graft failure (GF) and minimal GvHD rates.

T-cell replete cord transplants give superior outcomes in high-risk and relapsed/refractory pediatric myeloid malignancy.

Stem cell transplant (SCT) outcomes in high-risk and relapsed/refractory (R/R) pediatric acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) have been historically poor. Cord blood (CB) allows T-cell replete CB transplant (TRCB), enabling enhanced graft-versus-leukemia. We consecutively collected data from 367 patients undergoing TRCB (112 patients) or other cell source (255 patients) SCT for pediatric AML/MDS in the United Kingdom and Ireland between January 2014 and December 2021. Data were collected about the patient's demographics, disease, and its treatment; including previous transplant, measurable residual disease (MRD) status at transplant, human leukocyte antigen-match, relapse, death, graft versus host disease (GvHD), and transplant-related mortality (TRM). Univariable and multivariable analyses were undertaken. There was a higher incidence of poor prognosis features in the TRCB cohort: 51.4% patients were MRD positive at transplant, 46.4% had refractory disease, and 21.4% had relapsed after a previous SCT, compared with 26.1%, 8.6%, and 5.1%, respectively, in the comparator group. Event free survival was 64.1% within the TRCB cohort, 50% in MRD-positive patients, and 79% in MRD-negative patients. To allow for the imbalance in baseline characteristics, a multivariable analysis was performed where the TRCB cohort had significantly improved event free survival, time to relapse, and reduced chronic GvHD, with some evidence of improved overall survival. The effect appeared similar regardless of the MRD status. CB transplant without serotherapy may be the optimal transplant option for children with myeloid malignancy.

Pre-transplant myeloid and immune suppression, upfront plerixafor mobilization and post-transplant cyclophosphamide: novel strategy for haploidentical transplant in sickle cell disease.

Allogenic hematopoietic stem cell transplant is the only curative option for symptomatic sickle cell disease (SCD). HLA haploidentical related donor transplants are associated with high graft failure rates. We conceptualized a novel protocol (APOLLO protocol) using pre-transplant immune and myelosuppression (PTIS) using fludarabine, cyclophosphamide, and dexamethasone followed by augmented John Hopkins protocol by adding thiotepa to conditioning. Twenty-five consecutive patients suffering from symptomatic SCD were enrolled into the study. We added upfront plerixafor to granulocyte colony stimulating factor (GCSF) for mobilization of healthy donors. Graft versus host disease (GvHD) prophylaxis was done using post-transplant cyclophosphamide, sirolimus, and mycophenolate mofetil. Graft failure was not seen in any of our patients. Five patients developed acute grade II/IV GvHD (4 classical acute, 1 late onset), 3 had limited chronic GvHD. Out of 25 evaluable patients, 22 are alive and disease free, making an overall survival (OS) and disease-free survival (DFS) of 88% with a median follow up of 485 days (range 198-802). T-cell-replete haploidentical transplant with PTIS, augmented John Hopkins conditioning and plerixafor based mobilization is a safe and effective way of treating patients suffering from SCD with minimal or no risk of graft failure and acceptable GvHD rates.