Hodgkin Disease Patients. Following High-Dose. Busulfan, Etoposide,. Cyclophosphamide, and. Autologous Stem Cell. TransplantationâA. Similar Experience.
Biology of Blood and Marrow Transplantation 13:746-747 (2007) 䊚 2007 American Society for Blood and Marrow Transplantation 1083-8791/07/1306-0001$32.00/0
LETTER
TO THE
Long-term Outcome of Hodgkin Disease Patients Following High-Dose Busulfan, Etoposide, Cyclophosphamide, and Autologous Stem Cell Transplantation—A Similar Experience In December 2006, Wadehra et al. [1] 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 eto-
Figure 1. Kaplan-Meier estimates of survival. Autologous stem cell transplant in Hodgkin’s disease using high dose busulfan, cyclophosphamide, and etoposide preparative regimen.
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EDITOR
Table 1. Patient Characteristics Median age in years (range) Male vs. female (%) Disease status: CR/PR vs. refractory (%) Stem cell source: bone marrow vs. PBSC (%) Number of prior chemotherapy regimens (median)
32 (19-64) 58% vs. 42% 48% vs. 52% 13% vs. 87% 3
CR indicates complete remission; PR, partial remission; PBSC, peripheral blood stem cell.
poside 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. At our institution, we have administered busulfan to achieve a total area under the curve (AUC) of 20,000 mol ⫻ min/L, integrated over all doses (2-4). 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 admin-
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Letter to the Editor
istered 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.
REFERENCES 1. Wadehra 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;12:1343-1349. 2. Slattery JT, et al. Marrow Transplantation for Chronic Myeloid
Leukemia: The Influence of Plasma Busulfan Levels on the Outcome of Transplantation. Blood, Vol 89. April 1997. 3. Anderson BS, 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: 477-485. 4. Bolinger AM, 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.
Eric C. Santos Jolynn Sessions Don Hutcherson Christopher Flowers Amelia Langston Edmund K. Waller Department of Hematology and Oncology Bone Marrow Transplant Unit Emory University Hospital Atlanta, Georgia
Biology of Blood and Marrow Transplantation 13:746-747 (2007)
doi:10.1016/j.bbmt.2007.02.006
Erratum In the article entitled “Human Progenitor Cells Rapidly Mobilized by AMD3100 Repopulate NOD/SCID Mice with Increased Frequency in Comparison to Cells from the Same Donor Mobilized by Granulocyte Colony Stimulating Factor” by Hess et al., in the April 2007 issue of Biology of Blood and Marrow Transplantation (Volume 13, Number 4, pages 398-411), the third author’s name should have been Timothy P. Craft (not Timothy C. Craft).
