Days In Arm Research Articles

A Prospective Randomized Trial of Buffy Coat Versus CD34-Selected Autologous Bone Marrow Support in High-Risk Breast Cancer Patients Receiving High-Dose Chemotherapy

High-dose chemotherapy with hematopoietic progenitor cell support is administered increasingly to selected categories of patients with high-risk malignancies. Bone marrow and/or peripheral blood progenitor cells (PBPCs) are commonly cryopreserved with the cryoprotectant dimethyl sulfoxide (DMSO), which can cause a variety of systemic side effects when the graft is thawed and infused. The progenitor cells thought to be responsible for hematopoietic recovery express the CD34 antigen and constitute 1% to 3% of the marrow cells and 0.5% of the PBPC fraction. Transplantation of a CD34(+) graft would markedly reduce the volume and thus the amount of DMSO required, thereby decreasing the infusion-related toxicities. In this study, 89 high-risk breast cancer patients received high-dose therapy and were randomized to receive an autologous CD34(+) marrow graft (Arm A) versus a standard buffy coat fraction (Arm B). After marrow infusion, significant increases in diastolic and systolic blood pressure, as well as significant decreases in heart rate, were documented in Arm B compared to Arm A patients (P < .001). None of the patients in Arm A experienced any clinically serious adverse events associated with the marrow infusion compared to 6% of the Arm B patients. The median time to neutrophil engraftment was 13 days for Arm A and 11 days for Arm B patients (P = .218). The median time to platelet engraftment was 27 days for Arm A and 20 days for Arm B patients (0.051). There were no other significant differences between the two arms of the study with respect to thrombocytopenia-related complications or immune function reconstitution. Additionally, patients on Arm A who received >/=1.2 x 10(6) CD34(+) cells/kg had no delay in platelet recovery (22 days), compared to patients on Arm B, who also received greater than 1.2 x 10(6) CD34(+) cells/kg (20 days) (P = .604). In conclusion, this prospective randomized study demonstrates that breast cancer patients who receive high-dose therapy with autologous CD34(+) marrow support have reduced marrow infusion-related toxicity, comparable time to neutrophil engraftment and immune function recovery posttransplant, and for those who receive <1.2 x 10(6) CD34(+) cells/kg, comparable time to platelet engraftment compared to women who receive buffy coat fractions of marrow.

A Prospective Randomized Trial of Buffy Coat Versus CD34-Selected Autologous Bone Marrow Support in High-Risk Breast Cancer Patients Receiving High-Dose Chemotherapy

AbstractHigh-dose chemotherapy with hematopoietic progenitor cell support is administered increasingly to selected categories of patients with high-risk malignancies. Bone marrow and/or peripheral blood progenitor cells (PBPCs) are commonly cryopreserved with the cryoprotectant dimethyl sulfoxide (DMSO), which can cause a variety of systemic side effects when the graft is thawed and infused. The progenitor cells thought to be responsible for hematopoietic recovery express the CD34 antigen and constitute 1% to 3% of the marrow cells and 0.5% of the PBPC fraction. Transplantation of a CD34+ graft would markedly reduce the volume and thus the amount of DMSO required, thereby decreasing the infusion-related toxicities. In this study, 89 high-risk breast cancer patients received high-dose therapy and were randomized to receive an autologous CD34+ marrow graft (Arm A) versus a standard buffy coat fraction (Arm B). After marrow infusion, significant increases in diastolic and systolic blood pressure, as well as significant decreases in heart rate, were documented in Arm B compared to Arm A patients (P < .001). None of the patients in Arm A experienced any clinically serious adverse events associated with the marrow infusion compared to 6% of the Arm B patients. The median time to neutrophil engraftment was 13 days for Arm A and 11 days for Arm B patients (P = .218). The median time to platelet engraftment was 27 days for Arm A and 20 days for Arm B patients (0.051). There were no other significant differences between the two arms of the study with respect to thrombocytopenia-related complications or immune function reconstitution. Additionally, patients on Arm A who received ≥1.2 × 106 CD34+ cells/kg had no delay in platelet recovery (22 days), compared to patients on Arm B, who also received greater than 1.2 × 106 CD34+ cells/kg (20 days) (P = .604). In conclusion, this prospective randomized study demonstrates that breast cancer patients who receive high-dose therapy with autologous CD34+ marrow support have reduced marrow infusion-related toxicity, comparable time to neutrophil engraftment and immune function recovery posttransplant, and for those who receive <1.2 × 106 CD34+ cells/kg, comparable time to platelet engraftment compared to women who receive buffy coat fractions of marrow.

248 Growth factors in combination: Phase I study of dose intensified carboplatin (CB), cyclophosphamide (CT) and etoposide (VP) in patients (PTS) with advanced, refractory cancer

This phase I study was designed in order to verify the toxicity of CB. CTX, VP given at high doses, in combination with GCSF alone or GCS and GMCSF given sequentially. The two lymphokines, with different properties, might have their ideal integration in the sequential administration. A group of 10 heavily pretread patients (PTS) with stage IV disease (2 breast cancer, 2 small cell and 1 non small cell lung cancer, 1 sarcoma, 1 colorectal cancer, 1 ependymoblastorna, 1 signet-ring cell bladder cancer, 1 neuroendocrine prostate cancer) were enrolled into the study between August and September 1994. Median (M) PS (ECOG) was 1, M age 41 years (22–65). Previous treatments: 7 PTS had surgery, 4 PTS had radiotherapy, all PTS had received previously a median of 4. 5 chemotherapy courses (4–12). CB-CTX-VP combination was administered over 3 days. Each patient, received two courses of the same CT, followed, randomly, either by 14 days of GCSF (arm A) or by 7 days of GCSF and 7 days of GMCSF (arm B) with cross over in the second CT course. Both growth factors were given sq at the dose of 5μg/kg/day. CB dose was calculated according to Calvert et al. (JCO 1989,7:1748) and expressed with the area under the concentration versus time curve (AUC). All patients received an outpatient treatment. The maximum tolerated doses of CTX and Vp, found in a previous work (Ann Oncol 1994, 5:90,), were, respectively, 1500 and 400mg/m2, while CB doses ranged from 5 to 8 AUC. Twenty chemotherapy courses over 20 are evaluable. Absolute neutrophil count (ANC)<1000μL for 54 days in arm A versus 68 days in arm B (<i>P</i>=0.02); platelets (PLT) count<25.000μL: 57 days arm A versus 30 days in arm B (<i>P</i>=0.03); days of hospitalisation 35 in arm Aversus 16 in arm B (<i>P</i>=0.75); platelets transfusion: 107 Vs 58 (<i>P</i>=0.02); PRBCS 15 vs 5 (<i>P</i>=0.25). No treatment related death occurred. At the present time, eight patients had responses and are alive. These data indicate that dose intensified CT may be delivered safely; GCSF alone shortens days of neutropenia, the combination of the 2 cytokines shortens the time of thrombocytopenia and decreases the number of platelets transfusions.