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CORRESPONDENCE Reduced-intensity conditioning has in the last few years
revolutionized allogeneic hematopoietic stem cell transplantation (allo-HSCT).1-6 The reduced toxicity has extended its
availability to groups of patients hitherto ineligible because of
advanced age or comorbidity. Alemtuzumab (CAMPATH-1H) has been used
successfully for in vivo T-cell depletion, reducing the incidence of
graft-versus-host-disease (GVHD) and preventing graft
rejection.7-10 We have performed 60 reduced-intensity allo-HSCT procedures in
myelodysplastic syndromes and acute myeloid leukemia, using conditioning with 30 mg/m2 fludarabine administered
intraveneously each day, days Kaplan-Meier analysis predicts that to day 300, of the 32.8% overall
mortality, 43% would occur between day 100 and day 200. Similarly, of
the TRM of 24.7% and disease-free survival (DFS) of 46%,
52%, and 40%, respectively, would occur within the second hundred
days (Figure
1A).
The incidence of GVHD (before donor lymphocyte infusion) in sibling and VUD recipients was 26.1% (6 of 23 patients) and 21.6% (8 of 37 patients), with a median time to onset of 43 days (range, 39-100 days) and 19 days (range, 14-131 days), respectively. There were no grades III-IV GVHD. All sibling recipient-donor pairs were fully human leukocyte antigen (HLA) matched at 6 loci, while 12 of 44 VUD recipient-donor pairs were disparate (10 HLA class I mismatches; 1 class II; 1 class I and II). Four of these patients received a graft with a major HLA mismatch. Although the median time of onset of GVHD and CMV viremia occurred within the first 100 days, the major events marking overall survival, TRM, and relapse all have a median onset at day 100 in the second 100 days after transplantation, with no plateau in the survival curves. In conventional myeloablative HSCT, day 100 has traditionally
been a temporal landmark, with the plateau in survival curves (Figure 1B). Although the conventional and reduced-intensity HSCT groups are not comparable because of age and other major differences, especially concerning comorbid medical conditions, with
reduced-intensity allografts the plateaus appear to occur much later
(Figure 1A), accounted for by delayed TRM and relapse (Tables
2-3).
Although day 100 will remain a useful comparator, is day 200 or day
300 a more appropriate landmark in reduced-intensity allografts?
We suggest authors consider reporting these time points in
reduced-intensity studies, as we believe that this would then include
the highest risk period and reflect more accurately the eventual
outcome.
Aloysius Y. L. Ho, Michelle Kenyon, Ihab El-Hemaidi, Stephen Devereux, Antonio Pagliuca, and Ghulam J. Mufti
References
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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.
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1998;91:756-763 2. Nagler A, Slavin S, Varadi G, Naparstek E, Samuel S, Or R. Allogeneic peripheral blood stem cell transplantation using a fludarabine-based low intensity conditioning regimen for malignant lymphoma. Bone Marrow Transplantation. 2000;25:1021-1028[CrossRef][Medline] [Order article via Infotrieve]. 3. Bacigalupo A. Hematopoietic stem cell transplants after reduced intensity conditioning regimen (RI-HSCT): report of a workshop of the European group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplantation. 2000;25:803-805[CrossRef][Medline] [Order article via Infotrieve]. 4. Martino R, Caballero MD, Canals C, et al. Allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results of a prospective multicentre study. Br J Haematol. 2001;115:653-659[CrossRef][Medline] [Order article via Infotrieve].
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Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies.
Blood.
2002;99:75-82 7. Hale G, Jacobs P, Wood L, et al. CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells. Bone Marrow Transplant. 2000;26:69-76[CrossRef][Medline] [Order article via Infotrieve].
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Chakraverty R, Peggs K, Chopra R, et al.
Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen.
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Kottaridis PD, Milligan DW, Chopra R, et al.
In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation.
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Buggins AGS, Mufti GJ, Salisbury J, et al.
Peripheral blood but not tissue dendritic cells express CD52 and are depleted by treatment with alemtuzumab.
Blood.
2002;100:1715-1720   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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