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The optimal myeloablative conditioning regimen for ALL patients undergoing hematopoietic cell transplant (HCT) with an alternative donor is unknown. We analyzed HCT outcomes ALL patients (n= 269) who underwent HCT at our center from 2010 to 2020 in complete remission (CR) after FTBI-etoposide and CNI-based GvHD prophylaxis for matched donor HCT (ETOP-package; n= 196) or FTBI-Fludarabine and post-transplant cyclophosphamide (PTCy)-based prophylaxis for HLA- mismatched (related or unrelated) donors (FLU-package; n= 64). Patients in FLU-package showed a significant delay in engraftment (p< 0.001) and lower cumulative incidence (CI) of any and extensive chronic GVHD (p= 0.009 and 0.001, respectively). At the median follow up of 4.6 years (range 1–12 years); non-relapse mortality, overall or leukemia-free survival and GVHD-free/relapse-free survival were not significantly impacted by the choice of conditioning. However, in patients at CR2 or with measurable residual disease (MRD+), there was a trend towards higher relapse after FLU-package (p= 0.08 and p= 0.07, respectively), while patients at CR1 regardless of MRD status had similar outcomes despite the package/donor type (p= 0.9 and 0.7, respectively). Our data suggests that FLU-package for alternative donors offers comparable outcomes to ETOP-package for matched donor HCT to treat ALL. Disease status and depth of remission at HCT were independent predictors for better outcomes.

Post-transplant cyclophosphamide (PTCy) combined with tacrolimus (TAC) as graft-versus-host disease (GvHD) prophylaxis post-hematopoietic cell transplantation (HCT) is safe and effective. Optimal serum levels of TAC in this combination remain undetermined. We hypothesized that TAC at initial steady state (TISS) of <10 ng/mL could promote optimal transplant outcomes and prevent TAC-associated toxicities. We retrospectively analyzed a consecutive case series of 210 patients who received PTCy/TAC-based prophylaxis post-HCT from 1/2013-6/2018. Patients received HCT from haploidentical (n= 172) or mismatched donors (n= 38), and flat dose (FD) or weight-based dose (WBD) TAC. Twenty-four-month overall survival (OS), disease free survival (DFS), and relapse rate (RR) were 61%, 56%, and 22%, respectively, in TISS < 10 ng/mL cohort (n= 176), and 50%, 43%, and 35%, respectively, in TISS ≥ 10 ng/mL cohort (n= 34) (OS, P= 0.71; DFS, P= 0.097; RR, P= 0.031). OS, DFS, RR, non-relapse mortality, acute GvHD grade II–IV, grade III–IV or chronic GvHD by TISS were similar in multivariable analysis. TISS ≥ 10 ng/mL conferred increased risk of viral infection (P= 0.003). More patients receiving FD vs. WBD had TISS < 10 ng/mL (P= 0.001). Overall, TISS < 10 ng/mL early post HCT conferred similar survival outcomes and lowered risk of viral infection and toxicities compared to TISS ≥ 10 ng/mL.

Allogeneic hematopoietic cell transplantation (alloHCT) is the only curative therapy for primary myelofibrosis (MF) as well as myelofibrosis secondary to other myeloproliferative neoplasms (MPN). Pulmonary hypertension (PH) is a known complication of MF and may occur in up to 50% of such patients. PH (defined as a mean pulmonary artery pressure ≥25 mmHg at rest) can eventually lead to right heart failure and may be associated with complications after alloHCT. We examined the association of PH with alloHCT outcome in patients with MF associated with MPN. Pre- and post-HCT echocardiograms were reviewed to estimate the peak pulmonary artery systolic pressure (PASP). Median PASP was 37.0 mmHg (range: 16.0-57.9) prior to HCT with 37 of 65 patients (57%) studied. With median follow-up of 35.0 months (range: 3.3–119.4) PH was significantly associated with inferior OS (58.9% vs. 88.8%, P= 0.025), primarily due to increased NRM (21.6% vs. 7.1%, P= 0.007). The majority of the deaths (8 of 14) in patients with PH occurred within 100 days after HCT. In patients with an available post-HCT echocardiogram (n= 33), the median PASP was 30 mmHg (range: 5.0–56.2); eight patients (24%) had persistent PH. Compared with pre-HCT values, PASP was significantly reduced after HCT (p< 0.001). We conclude that PH is associated with inferior survival due to the increased NRM in patients with MF undergoing alloHCT. PH appears at least partially reversible after successful alloHCT. PH should be considered a risk factor for early mortality after alloHCT and surveillance of pulmonary artery pressure in MF patients being considered for alloHCT may be useful.