The Criteria for Bone Marrow Recovery Post–Myelosuppressive Therapy for Acute Myelogenous Leukemia: A Quantitative Study

Abstract

Abstract Context.—Although the early post–myelosuppressive chemotherapy pathologic changes of the marrow have been described, the rate and the histologic definition of recovery are not defined. Objective.—To study the rate of recovery of bone marrow in patients given myelosuppressive therapy for acute myelogenous leukemia, establish the histologic criteria of recovered marrow, and correlate the recovery pattern with those patients who received a bone marrow transplant by using histology, peripheral blood, immunophenotyping, and computerized morphometry and mathematical slope equation. Design.—We studied the post–myelosuppression recovery of the bone marrow to determine patterns and rate of recovery in 135 serial bone marrow biopsies of 51 patients. These patients were divided into 2 groups: 1 group of 28 cases diagnosed with acute myeloid leukemia, the majority treated with cytarabine (Ara-C) infusion for 7 days and daunorubicin intravenously daily for 3 days (7+3 regimen), and the other control group of 23 cases treated with chemotherapy or allogeneic bone marrow transplantation for a variety of hematologic malignancies. All biopsies during the recovery period were obtained before consolidation regimen. We used morphometry to calculate the cellularity and myeloid to erythroid ratio and quantified megakaryocytes CD10 versus time from day 14 onward. The absolute neutrophil and platelet counts for 28 cases were related to histologic recovery. Results.—From day 14, we noted a differential slope of recovery of these patients with no difference in male and female patients, P = .45, but a difference between younger and older patients (>58.5 years), P = .03. After regenerative hyperplasia, the cellularity plateaus, the myeloid to erythroid ratio, and the megakaryocytes even out with platelet normalization, and the early CD10+ B cells rise from day 40 onward, P = .01. The patterns of recovery after day 60 of postchemotherapy and posttransplantation patients are similar. Complete histologic and peripheral blood recovery is noted at day 38 and thereafter. Conclusions.—By linear equation using at least 2 trephine biopsy specimens, the projected rate of cellular recovery may be determined, and 5 histologic features are associated with complete histologic recovery.