Usefulness of 3 Monthly Marrow Evaluations in Predicting Relapse of Myeloid Malignancies After HCT

INTRODUCTION:Optimal sampling interval, sample source and technique to detect impending relapse after hematopoietic cell transplantation (HCT) is not well-defined. For most myeloid malignancies (except CML) donor chimerisms, peripheral blood parameters, and bone marrow cytomorphology are the main options for disease detection post-HCT. The role of molecular markers is still evolving.  The aim of our study is to evaluate the usefulness of 3 monthly bone marrow (BM) evaluations for the first year after HCT using these techniques in predicting relapse.

METHODS: A retrospective review of the patients who relapsed following an allogeneic HCT for a myeloid malignancy at Mayo Clinic in Arizona was performed. The BM sample closest in time prior to relapse was identified and the morphologic, flow cytometric, karyotypic, FISH, PCR and chimerism results were reviewed.

RESULTS: Out of 187 patients with a myeloid malignancy, 40 (31 AML, 4 MPN blast crisis, 4 MDS, 1 CML) relapsed at a median of 113 days (range 22-820 days) after HCT. Thirty percent of the relapses occurred after a myeloablative HCT. Donor type was equally distributed between matched related and mismatched/ matched unrelated donors. A cytogenetic and molecular marker with the diagnosis was identifiable in 22/40 and 6/40 patients respectively. 18/40 patients had residual disease present at HCT. 13/40 patients showed an early relapse within the first 90 days. In the remaining patients, time between the last BM and relapse ranged from 38-184 days (median 69). Abnormal results were found only in 9/27 patients in the preceding BM and included abnormal cytogenetic clone identical to diagnosis in 2 patients; abnormal RT-PCR for BCR/ABL in 1, cytogenetic abnormality in donor cell line in 3, and decreased chimerisms in unsorted marrow cells in 3 patients.

CONCLUSIONS: A 3-month monitoring schedule of BM evaluation using the currently available tools had low sensitivity to predict relapse. Findings that may justify intervention were rare (less than 10% of patients), and were restricted to abnormal cytogenetic and abnormal RT-PCR results. The clinical significance of cytogenetic abnormalities observed in donor cells is not clear. Our findings emphasize that until the optimal surveillance technique and schedule can be defined and standardized, more frequent use of pre-emptive therapy in patients at high risk of relapse may be of benefit.