Collaborations with Hematologic Malignancy Committees:
AAML05P1: Relapse and GVHD rates are lower following ex vivo T-cell depleted HCT from KIR mismatched donors.26 The impact of KIR mismatch without T-cell depletion has been mixed.27, 28 AAML05P1 determined that KIR match can be determined prior to donor selection for pediatric patients with acute myelogenous leukemai (AML; n=90), but KIR mismatch does not improve survival, DFS, or relapse following in vivoT-cell depleted HCT.28
AAML1031: Allogeneic HCT from the best available donor improves survival for patients with AML who have high-risk cytogenetics or mutation profiles, such as Fms-like tyrosine kinase (FLT3) mutations.29, 30 Among other research questions, AAML1031 tested whether adding sorafenib, a tyrosine kinase inhibitor (TKI) that inhibits constitutively activated FLT3 during induction and maintenance would improve outcomes for patients with high allelic ratio (AR >0.4) mutated FLT3. Patients who were not treated with sorafenib (n=76) had worse DFS (HR 2.28, p=0.032) than patients who were treated with sorafenib (n=72). Although more patients who received sorafenib underwent allogeneic HCT (64% vs 25%, p<0.001), the benefit of sorafenib was confirmed by multivariate analysis that accounted for HCT use and concurrent favorable co-mutations.31
AALL1331: A CT-ALL collaboration standardized the HCT approach for ALL and showed that two cycles of blinatumomab improved survival and decreased toxicity compared to intensive chemotherapy prior to HCT for relapsed ALL, establishing a new standard of care.32The survival advantage from blinatumomab was likely a result from more patients achieving a suitable remission status and receiving HCT. Future trials should test whether patients should proceed directly to HCT after 1 cycle of blinatumomab if they have achieved MRD negativity.
ANHL1522: A CT-NHL collaboration evaluated “off the shelf” Epstein Barr virus (EBV) specific T cells for the treatment of post-transplant lymphoproliferative disease (PTLD) refractory to rituximab in pediatric solid organ transplant (SOT) recipients. The trial was closed early after 15 of a planned 30 patients enrolled due to slow accrual. Administering novel T-cell therapies in a cooperative group setting was feasible but too few patients were studied to assess efficacy (NCT02900976).