Long-term Outcome of Hodgkin Disease Patients Following High-Dose Busulfan, Etoposide, Cyclophosphamide, and Autologous Stem Cell Transplantation—A Similar Experience
Year: 2007
Type: article
Abstract: In December 2006, Wadehra et al. [1Wadehra N. Farag S. Bolwell B. et al.Long-term outcome of Hodgkin disease patients following high-dose busulfan, etoposide, cyclophosphamide, and autologous stem cell transplantation.Biol Blood Marrow Transplant. 2006; 12: 1343-1349Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar] reported on the long-term outcome of Hodgkin’s Disease patients after autologous stem cell transplant using a high dose busulfan, cyclophosphamide, etoposide preparative regimen. With a median follow-up of 6.7 years, the 5-year progression-free survival (PFS) was 48% and 5-year overall survival (OS) was 51%. We have had a similar experience with essentially the same preparative regimen at Emory University. Our 5-year OS was 55%, with a median follow-up of 2 years for surviving patients (see Figure 1). During the period of 1995 to 2005, we used the combination of busulfan, cyclophosphamide, and etoposide as a conditioning regimen for 71 consecutive patients with Hodgkin’s lymphoma undergoing autologous hematopoietic progenitor cell transplantation. Median patient age was 32 years (range 19-64 years), and 58% of patients were male. The source of progenitor cells was bone marrow for 9 and blood stem cells for 62 patients (see Table 1). Forty-eight percent of patients had achieved a complete remission (CR) or partial remission (PR) at the time of transplant; the remainder had refractory disease. The median number of chemotherapy prior to high-dose chemotherapy was 3.Table 1Patient CharacteristicsMedian age in years (range)32 (19-64)Male vs. female (%)58% vs. 42%Disease status: CR/PR vs. refractory (%)48% vs. 52%Stem cell source: bone marrow vs. PBSC (%)13% vs. 87%Number of prior chemotherapy regimens (median)3CR indicates complete remission; PR, partial remission; PBSC, peripheral blood stem cell. Open table in a new tab CR indicates complete remission; PR, partial remission; PBSC, peripheral blood stem cell. At our institution, we have administered busulfan to achieve a total area under the curve (AUC) of 20,000 μmol × min/L, integrated over all doses (2Slattery J.T. et al.Marrow Transplantation for Chronic Myeloid Leukemia: The Influence of Plasma Busulfan Levels on the Outcome of Transplantation.Blood. 1997; Vol 89 (April)Google Scholar, 3Anderson B.S. et al.Busulfan Systemic Exposure Relative to Regimen-Related Toxicity and Acute Graft-versus-Host Disease: Defining a Therapeutic Window for IV BuCy2 in Chronic Myelogenous Leukemia.Bio Blood Marrow Transplant. 2002; 8: 477-485Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar, 4Bolinger A.M. et al.An Evaluation of Engraftment, Toxicity and Busulfan Concentration in Children Receiving Bone Marrow Transplantation for Leukemia or Genetic Disease.Bone Marrow Transplantation. 2000; PubMed Google Scholar). Oral busulfan was used between March 1995 and May 2004, initiated at a dose of 1 mg/kg by mouth every 6 hours × 16 doses. In May 2004 we began using i.v. busulfan, initiated at 0.9 mg/kg i.v. every 6 hours × 16 doses starting on day −8. Sequential busulfan levels were obtained with the first dose, and the AUC was calculated using the trapezoidal rule. Busulfan doses were adjusted to obtain the targeted levels. Etoposide was given at a dose of 10 mg/kg/dose every 24 hours on days −4, −3, and −2, and cyclophosphamide was given at a dose of 60 mg/kg every 24 hours on days −3 and −2. The median number of days to neutrophil engraftment was 12 days, and median time to platelet engraftment was 17 days. One hundred-day mortality occurred in 2 of 71 patients (3%), because of intracranial hemorrhage in 1 case, and infection in the other case. The incidence of veno-occlusive disease (VOD) using targeted Bu/Cy/VP16 was low; a concurrent analysis of 86 Hodgkin’s and non-Hodgkin’s lymphoma patients in 2004, who received targeted busulfan dosing, showed that the incidence of VOD was only 2.2%. Other regimen-related toxicities included grade 2-3 mucositis in the majority of patients. The recent addition of palifermin administered pre- and postconditioning has helped to reduce the incidence of mucositis associated with the Bu/Cy/VP16 regimen. Our institution’s experiences closely parallel the results reported by Wadehra et al. and further validate the toxicity and efficacy profile of this regimen. Posttransplant survival was favorable, considering that this population of patients was heavily pretreated, and half of them had refractory disease at the time of transplant. The low, 3% regimen-related 100-day mortality observed with this regimen, and the potential for accurate patient-specific targeting of busulfan levels offer the possibility that further dose escalation of busulfan may be possible in the setting of autologous stem cell transplantation. Long-term Outcome of Hodgkin Disease Patients Following High-Dose Busulfan, Etoposide, Cyclophosphamide, and Autologous Stem Cell TransplantationBiology of Blood and Marrow TransplantationVol. 12Issue 12PreviewBusulfan (Bu)-based preparative regimens have not been extensively investigated in Hodgkin disease (HD). The purposes of this study were to investigate the toxicity and efficacy of a novel preparative regimen of Bu 14 mg/kg, etoposide 50-60 mg/kg, and cyclophosphamide 120 mg/kg in patients with primary refractory and relapsed HD. One hundred twenty-seven patients with a median age of 33 years (range, 14-67 years) underwent transplantation. The regimen was well tolerated, with 5.5% treatment-related mortality at 100 days after transplantation. Full-Text PDF Open Archive
Institution: Emory University Hospital
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W1992816928