Posttransplant Thrombopoiesis Predicts Survival in Patients Undergoing Autologous Hematopoietic Progenitor Cell Transplantation

Abstract

The frequency and clinical significance of secondary thrombocytopenia following initial engraftment in autologous hematopoietic progenitor cell transplantation (HPCT) is unknown. An institutional review board approved retrospective study of thrombopoiesis was performed in 359 patients transplanted with autologous blood (97%) or marrow (3%) who achieved platelet engraftment to >50,000/microL. Idiopathic secondary posttransplant thrombocytopenia (ISPT) was defined as >50% decline in blood platelets to <100,000/microL in the absence of relapse or sepsis. ISPT occurred at a median of day +35 posttransplant in 17% of patients. Patients with ISPT had similar initial platelet engraftment (median 17 days) versus non-ISPT patients (18 days; P=NS) and recovered platelet counts (median 123,00 K/microL) by day 110 posttransplant. Four factors were independently associated with post-transplant death in a multivariate model: disease status at transplant; the number of prior chemotherapy regimens, failure to achieve a platelet count of >150,000/microL posttransplant, and the occurrence of ISPT. A prognostic score was developed based upon the occurrence of ISPT and posttransplant platelet counts of <150,000/microL. Survival of patients with both factors (n=25) was poor (15% alive at 5 years); patients with 1 factor (n=145) had 49% 5-year survival; patients with 0 factors (n=189) had 72% 5-year survival. Patients who failed to achieve a platelet count of >150,000/microL received significantly fewer CD34+ cells/kg (P<.001), whereas patients with ISPT received fewer CD34+CD38- cells/kg (P=.0006). The kinetics of posttransplant thrombopoiesis is an independent prognostic factor for long-term survival following autologous HPC. ISPT and lower initial posttransplant platelet counts reflect poor engraftment with long-term and short-term repopulating CD34+ hematopoietic stem cells, respectively, and are associated with an increased risk of death from disease relapse.

Characterization of hemopoietic engraftment kinetics and development of secondary cytopenia in AML post auto-SCT and its correlation with survival outcome

“…A significant proportion of our patients (n ¼ 30, 35.7%) developed a secondary decline in plt counts post transplantation. A similar observation was made by Ninan et al 26 in their study, in which the incidence of secondary thrombocytopenia was put at 17%, but their study was carried out in different groups of patients with various hematological malignancies who had AHSCT (18 cases of acute leukemias out of 62 patients). Also, the study by Bruno et al 27 on various malignancies reported an incidence of 19% among their autologous transplant patients.…”

“…26,27,[39][40][41] The immunological mechanism was explored by Ninan et al 26 in their study, but it did not show any autoimmune basis in their patients, neither was there any response in the plt counts with i.v. Ig administration.…”

“…26,28 Although the phenomenon has been well described among allogeneic transplant patients, very few reports are available in the literature for autologous transplant patients, more so in AML patients. 37,38 The few studies that have reported their observations on the effect of secondary thrombocytopenia on patients' survival and outcome in AML post-autologous transplantation had small numbers of AML patients in their study groups.…”

“…To identify the prognostic factors associated with survival and outcome of patients post AHSCT, the following variables, which were selected from earlier studies, 26,27 were evaluated: age of patient at transplant, patient's sex, cytogenetic abnormalities at diagnosis, sources of stem cells (BM vs peripheral blood) and total CD34 þ stem cells infused. Particular emphasis was put on analysis of engraftment kinetics of neutrophils, lymphocytes and plts, as well as any subsequent secondary decline of plt or neutrophil counts and their impact on survival outcome.…”

“…In addition, the phenomenon of 'secondary failure of plt recovery' or 'Idiopathic secondary post-transplant thrombocytopenia' described as a delayed decline in plt counts following an initial plt recovery, which is unassociated with either graft rejection, relapse or infection, has been reported to occur in patients who underwent hemopoietic SCT by many authors. [26][27][28] Thrombocytopenia typically occurs within the first 100 days post transplantation. Although there is availability of specific commercially prepared myeloid and erythroid growth factors for tackling posttransplant neutropenia and anemia, no such agent is yet available for the management of post-transplant thrombocytopenia.…”