Recovery from neutropenia can be predicted by the immature reticulocyte fraction several days before neutrophil recovery in autologous stem cell transplant recipients

Abstract

The duration of neutropenia (absolute neutrophil count (ANC) p100/ll) identifies cancer patients at risk for infection. A test that precedes ANCX100/ll would be of clinical value. The immature reticulocyte fraction (IRF) reflects erythroid engraftment and hence a recovering marrow. We evaluated the IRF as predictor of marrow recovery among 90 myeloma patients undergoing their first and second (75 patients) melphalan-based autologous stem cell transplantation (Mel-ASCT). The time to IRF doubling (IRF-D) preceded ANCX100/ll in 99% of patients after the first Mel-ASCT by (mean7s.d.) 4.2371.96 days and in 97% of the patients after the second Mel-ASCT by 4.1171.95 days. We validated these findings in a group of 117 myeloma patients and 99 patients with various disorders undergoing ASCT with different conditioning regimens. We also compared the time to hypophosphatemia and to absolute monocyte countX100/ll to the time to ANCX100/ll. These markers were reached prior to this ANC end point in 55 and 25% of patients but were almost always preceded by IRF-D. We conclude that the IRF-D is a simple, inexpensive and widely available test that can predict marrow recovery several days before ANCX100/ll.

Immature Reticulocyte Fraction and Absolute Neutrophil Count as Predictor of Hemopoietic Recovery in Patients with Acute Lymphoblastic Leukemia on Remission Induction Chemotherapy

“…In our study, mean recovery days were 11.84±7.44 for IRF and 17.67±8.77 for ANC, showing earlier IRF recovery by an average of 6 days, while it was shown to be 4 days earlier by Grazziutti et al [14]. This prediction of early recovery by the simple and reproducible parameter of IRF can have significant impact on the management of patients.…”

Determination of reference ranges for immature platelet and reticulocyte fractions and reticulocyte hemoglobin equivalent

“…Thus, they can be distinguished from the mature platelets and reticulocytes and quantified using RNA fluorescent labeling 1, 2, 3. Several studies have demonstrated the value of these indices in the context of hematopoietic stem cell transplantation as indicators of hematopoiesis, in transfusion assessment and the anticipation of successful engraftment 1, 2, 3, 4, 5, 6, 7, 8. The Ret-He is useful in the evaluation of hematopoiesis, with respect to the incorporation of iron 14, 15, 16, 17…”

“…They are important in various clinical situations, such as thrombocytopenia, anemia, bone marrow regeneration following the transplantation of hematopoietic stem cells and after chemotherapy 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13…”

Trial Design for Mold-Active Agents: Time to Break the Mold--Aspergillosis in Neutropenic Adults

“…Adults with a hematologic condition and (1) a reasonable chance of survival, (2) a reasonable chance of marrow recovery (e.g., those with acute leukemia, first remission induction chemotherapy, or high-risk autologous stem cell transplantation), (3) a likelihood of aspergillosis response (pulmonary, not disseminated aspergillosis), and (4) who have not received mold-active prophylaxis. Avoid postengraftment allogeneic stem cell transplantation (5) because of a high risk of data loss and protocol deviation (difficult logistics of care when patients are away from treating center), (6) because it could lead to a longer study period (longer delays and higher costs), (7) because outcome assessment could be complicated by graft-versus-host disease, changing immunosuppression, and higher death rates, and (8) because serum GMI has not been well validated in non-neutropenic contexts Limit patient heterogeneity, as above; the study should also enroll patients with single-organ aspergillosis (e.g., pulmonary aspergillosis) with positive serum GMI results and may later expand to include other populations/infection sites Stratify according to immune and disease status Use simple tests to predict neutropenia resolution; this should be done several days before the absolute neutrophil level is у100 cells/mL (e.g., immature reticulocyte fraction) [18] Standardize screening methods and schedules across enrolling sites Improve trial recruitment techniques: the study should include sponsor/investigator collaboration and training to maximize enrollment and to standardize GMI testing; establish GMI testing at all enrolling sites to ensure prompt results Challenges during recovery regard neutrophil recovery and reduction of immunosuppression Use a trial design aimed at enrolling patients during early neutropenia to mitigate immune reconstitution effect (e.g., IRIS) on outcome [12]. Antifungal prophylaxis [28,29] or preemptive (GMI-based) therapy [30] is preferred over treatment of clinically established aspergillosis, because GMI findings precede clinical/ radiologic findings [31][32][33][34], and prophylaxis and early therapy allow assessment of drug activity during severe immunosuppression Use frequent GMI testing (у3 times per week)…”

“…Variable immune recovery adds to heterogeneity after enrollment, with some patients experiencing prolonged neutropenia and others quickly recovering [18].…”