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Platelet Transfusion Requirements During Autologous Peripheral Blood Progenitor Cell Transplantation Correlate with the Pretransplant Platelet Count

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Platelet Transfusion Requirements During Autologous Peripheral Blood Progenitor Cell Transplantation Correlate with the Pretransplant Platelet Count Bone Marrow Transplantation, (1997) 20, 459–463 1997 Stockton Press All rights reserved 0268–3369/97 $12.00 Platelet transfusion requirements during autologous peripheral blood progenitor cell transplantation correlate with the pretransplant platelet count BJ Bolwell, M Goormastic, S Andresen, B Overmoyer, B Pohlman and M Kalaycio Department of Hematology and Medical Oncology, at the Cleveland Clinic Foundation, Cleveland, OH, USA Summary: after the infusion of autologous marrow.1,2 The use of primed peripheral blood progenitor cells (PBPC) has The use of primed peripheral blood progenitor cells resulted in more rapid platelet engraftment, with most trials (PBPC) has improved platelet engraftment following reporting platelet recovery in 14–18 days.3–8 Relatively few autologous bone marrow/PBPC transplantation series specifically report the number of platelet transfusions (ABMT). The thrombocytopenia associated with ABMT required during autologous transplantation when using generally lasts 14–18 days, and is associated with vari- PBPC. At our own institution, a median of five platelet able platelet transfusion requirements. Little, if any, transfusions are required during PBPC autologous trans- data exist examining prognostic parameters for platelet plantation. transfusion requirements during autologous transplan- Many studies have documented that both neutrophil and tation. We retrospectively examined 286 consecutive platelet engraftment correlates with the number of CD34+ patients undergoing autologous transplantation from 1 cells infused.9–12 However, little data exist examining other January l994 to 1 June l996 with respect to platelet potential prognostic parameters for platelet engraftment, or engraftment and platelet transfusion requirements. One for the number of platelet transfusion events required dur- hundred and fifty four patients were transplanted for ing autologous transplantation. Such parameters are neces- breast cancer (54%), 72 for non-Hodgkin’s lymphoma sary as new platelet stimulating agents, such as thrombopo- (25%), 35 for Hodgkin’s disease (12%), 13 for acute leu- ietin, are being incorporated into clinical trials. Anecdotal kemia (5%), eight for myeloma (3%), and four for other data from our institution suggested that patients beginning malignancy (1%). The median age was 44. All patients PBPC autologous transplant with a low platelet count received cytokine priming, usually with G-CSF, for the required more platelet transfusions during the transplant procurement of PBPC. The median number of CD34+ than did those patients beginning with a normal platelet cells collected was 4.3 × 106/kg. All patients received a count. To study this issue, we retrospectively examined 286 chemotherapeutic preparative regimen and all received consecutive patients undergoing autologous progenitor cell an autologous transplant using PBPC alone. The transplantation at our institution from 1 January l994 to median time to a platelet count of 20 × 109/l was 13 days. 1 June l996 to analyze whether the platelet count at the Patients beginning the transplant with a less than nor- time of transplantation correlated with either platelet mal platelet count (less than 150 × 109/l) engrafted in 17 engraftment, or the number of transfusion events required days, and received a median number of seven platelet during the transplant. transfusions, as compared with platelet engraftment of 12 days, and four platelet transfusions, for patients beginning the transplant with a normal platelet count Materials and methods (P = 0.001). Both groups of patients received an equiva- + lent dose of CD34 cells. We conclude that thrombocyto- Patient characteristics penia at the initiation of autologous transplantation is associated with increased platelet transfusion require- From 1 January l994 to 1 June l996, 286 consecutive adult ments, independent of the dose of CD34+ cells infused. patients underwent high-dose chemotherapy with autolog- Keywords: autologous marrow transplantation; stem ous progenitor cell transplantation at the Cleveland Clinic cells; platelet transfusions Foundation. Patient characteristics are shown in Table 1. PBPC collection and processing Platelet engraftment following autologous bone marrow All patients received cytokine priming for PBPC collection, transplantation (ABMT) historically occurred 4–5 weeks with G-CSF 5–10 mg/kg per day subcutaneously for 8–10 days, with PBPC collection beginning on day +5. Total × 6 + Correspondence: Dr BJ Bolwell, Cleveland Clinic Foundation, 9500 yield of PBPC collected was at least 2 10 CD34 cell/kg. Euclid Avenue, Cleveland, OH 44195, USA Prior to 1 March 1995, an acceptable alternative to the total + Received 30 December 1996; accepted 22 May 1997 CD34 count was 10 × 108 mononuclear cell/kg. The Platelet transfusion during PBPC autologous transplant BJ Bolwell et al 460 Table 1 Patient characteristics Group A Group B Total (low platelet count) (normal platelet count) No. of patients 74 212 Age (median) 44 44 44 Karnofsky status (pretransplant) % 90 90 90 Months from diagnosis to transplant (mean) 25 27 26 Preparative regimen (%) Bu-Cy-Vp 41 (55) 77 (36) 118 (41) Bu-Cy 9 (12) 36 (17) 45 (16) Ctx-Carbo-TT 18 (25) 76 (36) 94 (38) Ltx-Plat-BCNU 4 (5) 21 (10) 25 (9) Other 2 (3) 2 (1) 4 (1) Diagnosis (%) Breast cancer 29 (39) 125 (59) 154 (54) Non-Hodgkin’s lymphoma 23 (31) 49 (23) 72 (25) Hodgkin’s disease 10 (13) 25 (12) 35 (12) Acute leukemia 8 (11) 5 (2) 13 (5) Multiple myeloma 2 (3) 6 (3) 8 (3) Other 2 (3) 2 (1) 4 (1) Disease status of transplant (%) CR 46 (62) 131 (62) 177 (62) PR 26 (35) 76 (30) 102 (36) Refractory 2 (3) 5 (2) 7 (2) Bu-Cy-VP = busulfan, cyclophosphamide, etoposide; Bu-Cy = busulfan, cyclophosphamide; Ctx-Carbo-TT = cyclophosphamide, carboplatin, thiotepa; Ctx-Plat-BCNU = cyclophosphamide, cisplatin, BCNU. patients were harvested on a COBE Spectra leukapheresis generally for testicular cancer. G-CSF was routinely given machine (COBE, Denver, CO, USA). at a dose of 5 mg/kg per day beginning 4 h after the infusion of PBPC. G-CSF was discontinued after patients reached 9 3 + 1.0 × 10 /l neutrophils/mm on 2 consecutive days. CD34 analysis Peripheral blood progenitor cells obtained by apheresis Supportive care were collected into ACD-A anticoagulant. An aliquot of each collection was counted and a minimum of 20 × 106 Patients received prophylactic antibiotics consisting of oral cells were submitted for flow cytometric evaluation. For acyclovir, ciprofloxacin, and low-dose Amphotericin B (0.2 each sample, 250 000 events were required as list mode mg/kg), beginning on the day after PBPC infusion. Patients data using a Cell Quest (BDIS, San Jose, CA, USA) experiencing persistent fevers had their antibiotic coverage software document which had been specifically tailored and broadened. Patients received red blood cell transfusions to stored for this purpose. Total CD34+ cells were calculated maintain a hemoglobin greater than 9 gm/dl. Platelet trans- by multiplying the percentage of CD34+-positive cells in fusions were given for platelet counts less than 10 × 109/l the flow cytometric analysis by the total number of or for clinical bleeding. A platelet transfusion event was nucleated cells in the apheresis product. This number was either with single donor infusions, or pooled platelets divided by the patient’s actual weight to give the total (pooled platelets generally consisted of six pooled units CD34+ cells per kilogram. of platelets). Transplant protocol Definitions Ninety-nine percent of patients were treated with one of Platelet engraftment was defined as a platelet count of four chemotherapy (only) preparative regimens: cyclophos- 20 × 109/l independent of platelet transfusions. A platelet phamide, thiotepa, carboplatin (cyclophosphamide 1500 mg transfusion ‘event’ was any infusion of platelets, either per m2 daily × 4 days; thiotepa 125 mg per m2 daily × 4 pooled or a single donor. days; carboplatin 200 mg per m2 daily × 4 days); busulfan, For the purposes of this study, the platelet count was cyclophosphamide, VP-16, (busulfan 14 mg/kg, etoposide deemed normal (150 × 109/l or greater), or abnormal, on 50 mg/kg, cyclophosphamide 120 mg/kg); busulfan and the day of initiation of high-dose chemotherapy. Thus, all cyclophosphamide (busulfan 16 mg/kg, cyclophosphamide patients had already received cytokine priming and the col- 120 mg/kg); cyclophosphamide, cisplatin, BCNU lection of peripheral progenitor cells, at the time of evalu- (cyclophosphamide 1875 mg/m2 per day × 3 days; cisplatin ation of a normal or abnormal platelet count. The apheresis 55 mg/m2 per day × 3 days; BCNU 600 mg per m2). Four to collect CD34+ cells occurred 5–10 days prior to the patients (1%) received other chemotherapeutic regimens, initiation of the preparative regimen. Platelet transfusion during PBPC autologous transplant BJ Bolwell et al 461 Table 2 Prior chemotherapy and PBPC yield did group B. A multivariate analysis was then performed to examine factors related to days to engraftment. Age, sex, Group A Group B Total prior exposure to radiation therapy, number of courses of (low platelet (normal platelet prior chemotherapy, preparative regimen, diagnosis, CD34+ count) count) cell dose, and group A vs group B were included in the multiple regression model. This multivariate analysis found No. of patients 74 212 286 that the most important variable correlating with the time No. of courses of prior chemotherapy (%) + = 1 33 (44) 96 (46) 129 (45) to platelet engraftment was CD34 cell dose (P 0.004). 2
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