Dose-escalated cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) chemotherapy for patients with diffuse lymphoma: Cancer and Leukemia Group B studies 8852 and 8854.

BACKGROUND: To address the feasibility and outcome of moderate dose intensification with granulocyte-colony stimulating factor (G-CSF) for patients with aggressive non-Hodgkin lymphoma (NHL), the Cancer and Leukemia Group B (CALGB) conducted two studies evaluating dose-escalated cyclophosphamide and etoposide in the cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide (CHOPE) regimen. METHODS: Eligibility criteria included histologically documented, diffuse small cleaved, diffuse mixed, diffuse large cell, or immunoblastic lymphoma, Stage III--IV or bulky Stage II disease, and an ECOG performance status of 0--1. CALGB 8852, a group-wide study, accrued 227 patients: 120 patients in the pilot study to determine the maximum tolerated dose (MTD) without G-CSF and 107 in the pilot study of dose-escalated CHOPE with G-CSF. CALGB 8854, a limited-institution, Phase I study, enrolled 38 patients and determined the MTD of CHOPE with G-CSF to be used in CALGB 8852. The MTD in both studies was defined as the dose at which 50% of patients had 1) Grade 4 neutropenia or thrombocytopenia lasting 7 days or more, or 2) Grade 3--4 hemorrhage or nonhematologic toxicity (excluding alopecia, nausea, and emesis), or 3) were prevented from receiving 100% of drug on Day 22. RESULTS: The MTD of CHOPE without G-CSF was cyclophosphamide 1000 mg/m(2) on Day 1 and etoposide 100 mg/m(2) on Days 1--3 with doxorubicin 50 mg/m(2) on Day 1, vincristine 1.4 mg/m(2) (maximum, 2 mg) on Day 1, and prednisone 100 mg on Days 1--5. With the addition of G-CSF at 200 microg/m(2) on Days 5--19, the MTD was cyclophosphamide 1500 mg/m(2) and etoposide 160 mg/m(2) on Days 1-3 with standard doses of doxorubicin, vincristine, and prednisone. Increasing the dose of G-CSF from 200 microg/m(2) to 400 microg/m(2) did not allow for further dose escalation. The primary toxicity in all cohorts was neutropenia. Four toxic deaths occurred on CALGB 8852. The 5-year failure free survival (FFS) and overall survival (OS) rates for eligible patients on CALGB 8852 were 31% (95% confidence interval [95%CI], 23--39) and 48% (95%CI, 40--57), respectively. The 5-year FFS and OS rates for eligible patients on CALGB 8854 were 34% (95%CI, 17--52) and 51% (95%CI, 33--70), respectively. CONCLUSIONS: Moderate dose escalation with G-CSF is feasible. However, response and survival rates of patients who receive dose-escalated CHOPE, even with the addition of G-CSF, appear similar to the rates reported with standard-dose CHOP.

A dose escalation study of total body irradiation followed by high-dose etoposide and allogeneic blood stem cell transplantation for the treatment of advanced hematologic malignancies.

Since approximately 30% of leukemia patients relapse after allogeneic BMT using total body irradiation (TBI)-based preparative regimens, treatment intensity may be suboptimal. The killing of leukemia cells is proportional to the radiation absorbed dose. We studied the feasibility and toxicity of escalating the doses of fractionated TBI above our previous prescription of 13.5 Gy. Sixteen evaluable patients with advanced hematologic malignancies were treated with twice daily TBI using a high-energy source (18-24 MV). The first patient cohort (n = 11) received a total dose of 14.4 Gy in nine fractions, and the second cohort (n = 5) received doses escalated to 15.3 Gy. All patients received high-dose etoposide (60 mg/kg) and allogeneic stem cell transplantation following the TBI. All patients had HLA-identical sibling donors. The median times for neutrophil and platelet engraftment were 13.5 and 12 days, respectively, and did not differ between the two cohorts. All but one patient developed treatment-related grade 3 or 4 mucositis. There were three cases of grade 4 pulmonary toxicity and three cases of grade 4 hepatic toxicity among the 14.4 Gy cohort, and one case each of grade 4 pulmonary and hepatic toxicities among the 15.3 Gy cohort. In most cases comorbid conditions contributed to these toxicities. Two patients had significant GVHD of the GI tract. Six relapses occurred, five (45%) in the 14.4 Gy cohort and one (20%) in the 15.3 Gy cohort. The 100-day treatment-related mortality rates were 9% and 20% for the 14.4 Gy and 15.3 Gy cohorts, respectively, and the median survivals were 226 and 201 days, respectively. We conclude that TBI dose escalation above the previously used 13.5 Gy dose is feasible using a high-energy source and high-dose etoposide. Acute and chronic toxicities were primarily related to GVHD, infection and relapse rather than to TBI.

Allogeneic peripheral blood stem cell transplantation: clinical overview and nursing implications.

PURPOSE/OBJECTIVES: To provide a comprehensive understanding of allogeneic peripheral blood stem cell transplantation (PBSCT), the new modality for treating advanced hematologic malignancies. DATA SOURCE: Journal articles/abstracts, published literature, clinical experience. DATA SYNTHESIS: Growth factor mobilization and apheresis is well tolerated by donors and supplies adequate numbers of stem cells for engraftment. Patients engraft sooner using PBSCT compared to bone marrow transplant (BMT). CONCLUSIONS: Allogeneic PBSCT is a safe alternative to BMT and has distinct advantages for donors and recipients. Faster engraftment results in fewer transfusions, shorter hospitalization, and decreased cost. Future research to determine if long-term side effects from growth factors will negatively affect donors is essential. Data regarding durability of hematopoiesis and incidence of graft versus host disease warrant further analysis. IMPLICATIONS FOR NURSING PRACTICE: Care for patients is similar to that of standard BMT; however, care for donors is unique. Shorter hospitalization requires nurses to alter content and timing of patient education and preparation for discharge.