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).