Clinical trials of thrombopoietin (TPO), the central regulator of megakaryocytopoiesis, have revealed few side effects associated with its use. We here report a case of pancytopenia associated with the development of neutralizing antibodies to TPO that occurred in a patient who had undergone multicycle chemotherapy with multiple cycles of subcutaneous administration of pegylated recombinant human megakaryocyte growth and development factor. Samples of the patient's bone marrow showed trilineage hypoplasia with absence of myeloid, erythroid, and megakaryocyte progenitor cells but with elevated endogenous levels of erythropoietin, granulocyte colony-stimulating factor, and stem-cell factor. To our knowledge, this is the first report of an aplastic anemia-like syndrome associated with neutralizing antibodies to TPO. IntroductionTwo different forms of thrombopoietin (TPO) have entered clinical trials. 1 One is a recombinant form of the native molecule (rhTPO) and the other a pegylated, truncated version (pegylated recombinant human megakaryocyte growth and development factor [PEG-rHuMGDF]) with biologic activity similar to that of the native molecule. Early studies showed that both rhTPO 2 and PEG-rHuMGDF 3 are potent stimulators of thrombopoiesis and enhance platelet recovery when given after chemotherapy. 4,5 Both agents were reported to have minimal toxic effects; in particular, platelets produced after their administration function normally and have no evidence of activation. 2,5,6 Although antibodies to TPO were observed in the initial study of rhTPO, they were nonneutralizing and transient. 2 Here, we describe a case in which prolonged pancytopenia with neutralizing antibodies to TPO developed in a woman with ovarian cancer who had undergone 6 cycles of chemotherapy associated with administration of PEG-rHuMGDF. Study designGranulocyte-macrophage colony-forming cells, erythroid burst-forming units, and megakaryocyte colony-forming cells were assayed as described previously 7-9 by using freshly obtained bone marrow cells. Serum from the patient (stored at Ϫ20°C) was incubated with growth factors for in vitro cultures at 37°C for 60 minutes and examined for its activity on normal bone marrow cells. The highest concentration of patient's serum used was 10% of the final culture volume.Standard solid-phase sandwich enzyme immunoassays were used to measure serum levels of TPO, 10 granulocyte colony-stimulating factor (G-CSF), and erythropoietin (EPO) (R&D Systems, Minneapolis, MN). Cytokine levels were calculated from a standard curve generated by analysis of recombinant cytokines. Stem-cell factor (SCF) was assayed as described previously. 11 More than 200 samples of normal human serum were used to establish the SCF standard of 0.78 Ϯ 0.25 ng/mL (range, 0.29-1.62 ng/mL).Two established assays were used to detect neutralizing antibodies. The first was a solid-phase radioimmunoassay (RIA). 12 Reactivity was determined on the basis of the ratio of counts per minute in the posttreatment sample to the counts per mi...
Donor registries and transplantation societies recommend cryopreservation of unrelated donor hemopoietic progenitor cell (HPC) products before the recipient commences conditioning therapy to mitigate the donor and travel risks associated with the COVID-19 pandemic. However, little is known regarding the postthaw quality of such allogeneic products or the effect of precryopreservation storage and processing on these characteristics. We investigated the postthaw CD34+ cell recovery and viability of 305 allogeneic HPC products cryopreserved at 9 laboratories across Australia. Median postthaw CD34+ cell recovery was 76% and ranged from 6% to 122%. Longer transit time before cryopreservation, white cell count (WCC) during storage, and complex product manipulation before cryopreservation were independently associated with inferior postthaw CD34+ cell recovery. Longer precryopreservation transit time and WCC were also associated with inferior postthaw CD34+ cell viability. We conclude that although postthaw CD34+ cell recovery and viability of cryopreserved allogeneic HPC is generally acceptable, there is a significant risk of poor postthaw product quality, associated with prolonged storage time, higher WCC, and complex product manipulation precryopreservation. Awareness of expected postthaw recovery and practices that influence it will assist collection, processing, and transplant centers in optimizing outcomes for transplant recipients.
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