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Blood, 1 September 2004, Vol. 104, No. 5, pp. 1239-1240. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Abbott, B. L. Search for Related Content PubMed Articles by Abbott, B. L. Related Collections Related Article in Blood Online Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Comment on Diaconescu et al, page 1550 Do "minitransplantations" have "minitoxicity"? Brian L. Abbott UNIVERSITY OF MISSOURI AT KANSAS CITY Reduced intensity, or nonablative, conditioning regimens have made allogeneic hematopoietic transplantation available to patients ineligible for conventional ablative regimens. The rationale behind the nonablative approach rests on the theory that the curative aspect of allogeneic transplantation is mediated by a graft-versus-tumor effect rather than a high-dose cytotoxic effect. Since high-dose therapy is avoided, this approach was predicted to be safer for patients who were ineligible for conventional myeloablative regimens because of age or comorbidities. Investigators hypothesized that the early toxicity of high-dose regimens is caused by a combination of direct organ damage from the conditioning regimen as well as graft-versus-host disease (GVHD) provoked by a "cytokine storm" released from these damaged tissues. Although initial reports showed that successful donor engraftment is safely achievable with nonablative regimens, longer-term results of toxicities have thus far been lacking.1-3 Cumulative incidences of 1-year nonrelapse mortality among HC transplant recipients given nonablative versus ablative conditioning. See the complete figure in the article beginning on page 1550.   In this issue of Blood, Diaconescu and colleagues present a comparison of results using nonablative conditioning regimens with historic controls receiving conventional myeloablative transplants. Nonablative conditioning regimens consisted of either low-dose total body irradiation (TBI) only or the combination of fludarabine and TBI. Comorbidities were retrospectively measured by the Charlson comorbidity index, which was developed and validated as a measurement of mortality risk in breast cancer patients.4 This appears to be the first use of this scale to quantitate risk factors in recipients of hematopoietic cell transplants. Because of the incorporation of organ-specific functional assessments, this tool may provide additional power beyond nonspecific performance status assessments, such as the Eastern Cooperative Oncology Group score and Karnofsky scores. The authors present a systematic analysis of toxicities and the nonablative cohort experienced similar or lower toxicity rates for all parameters, with the exception of graft rejection. The authors conclude that despite the presence of higher levels of medical comorbidities, patients treated with nonablative allogeneic transplantation had significantly lower treatment-related mortality at 100 days and at 1 year after transplantation. A few cautionary notes are warranted. First, over half of the nonablative patients received TBI-only conditioning, a regimen not widely used in other centers. Second, data regarding longer-term follow-up are needed to determine if rates of disease control are similar with ablative and nonablative conditioning regimens; results of disease-related response, morbidity, and mortality are not included. It is possible that certain malignancies are more responsive to the allogeneic antitumor effect than others. Finally, although the onset of acute GVHD was delayed in the nonablative cohort, overall rates of severe acute GVHD were not lower, contrary to reports from other clinical investigators.5 The authors suggest this may have been due, in part, to a shorter course of cyclosporine GVHD prophylaxis in the nonablative cohort. Nonablative conditioning regimens will clearly retain a place among the available treatment options in allogeneic hematopoietic transplantation. Further work is needed to directly compare the results of nonablative and conventional conditioning regimens and to define the diseases for which the allogeneic graft-versus-malignancy effect is adequate for disease cure. As nonablative allogeneic transplantation becomes more common, formal systems of risk assessment such as the Charlson index might become an important tool for treatment decisions and patient selection, if these results are confirmed in prospective studies. References McSweeney PA, Niederwieser D, Shizuru JA, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood. 2001;97: 3390-3400.[Abstract/Free Full Text] Slavin S, Nagler A, Naparstek E, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998;91: 756-763.[Abstract/Free Full Text] Khouri IF, Keating M, Korbling M, et al. Transplantlite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol. 1998;16: 2817-2824.[Abstract] Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40: 373-383.[CrossRef][Medline] [Order article via Infotrieve] Couriel DR, Saliba RM, Giralt S. Acute and chronic graft-versus-host disease after ablative and nonmyeloablative conditioning for allogeneic hematopoietic transplantation. Biol Blood Marrow Transplant. 2004;10: 178-185.[CrossRef][Medline] [Order article via Infotrieve] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors Razvan Diaconescu, Christopher R. Flowers, Barry Storer, Mohamed L. Sorror, Michael B. Maris, David G. Maloney, Brenda M. Sandmaier, and Rainer Storb Blood 2004 104: 1550-1558. [Abstract] [Full Text] [PDF] Related Letter in Blood Online: Lessened severe graft-versus-host after "minitransplantations" Mohamed Sorror, Michael Maris, Razvan Diaconescu, and Rainer Storb Blood 2005 105: 2614. [Full Text] [PDF] This article has been cited by other articles: M. Sorror, M. Maris, R. Diaconescu, and R. Storb Lessened severe graft-versus-host after "minitransplantations" Blood, March 15, 2005; 105(6): 2614 - 2614. [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Abbott, B. L. Search for Related Content PubMed Articles by Abbott, B. L. Related Collections Related Article in Blood Online Related Letter in Blood Online Social Bookmarking                   What's this?

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