RESUMEN
We retrospectively evaluated the outcome of reduced-intensity conditioning (RIC) followed by allogeneic hematopoietic stem cell transplantation (HCT) in 43 patients with myelodysplastic syndrome (MDS) or AML arising from MDS. All patients received fludarabine plus melphalan followed by an allogeneic HCT from an HLA-identical sibling (SIB: n=19) or unrelated donor (MUD: n=24). Median age was 58 years (range: 30-71). Diagnoses at transplantation were RA (n=8), RARS (n=1), RAEB (n=13), RAEB-T (n=6), or AML arising from MDS (n=15). Of 28 patients with MDS, two patients had low, 10 had intermediate-1, nine had intermediate-2 and seven had high-risk MDS by IPSS criteria. All patients initially engrafted with the median neutrophil recovery of 15 days (range: 9-27). The 2-year overall survival, disease-free survival, relapse and transplant-related mortality were 53.5% (CI 45.2-61.1), 51.2% (CI 43.3-58.5), 16.3% (CI 7.9-30.7) and 35.2% (26.4-45.7), respectively. Grade II-IV acute graft-versus-host disease occurred in 27 (63%) patients. There was no significant survival difference between SIB and MUD-HCT, but the relapse rate was higher among SIB donor recipients when compared to MUD (38.5 versus 7%, P=0.02). RIC with fludarabine plus melphalan was associated with durable disease control and acceptable toxicity in this high-risk cohort.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Melfalán/uso terapéutico , Síndromes Mielodisplásicos/terapia , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Adulto , Anciano , Supervivencia de Injerto , Enfermedad Injerto contra Huésped , Enfermedades Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Melfalán/toxicidad , Persona de Mediana Edad , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/prevención & control , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento , Vidarabina/uso terapéutico , Vidarabina/toxicidadRESUMEN
We have utilized a human tumor colony forming assay to test the antitumor activity of 2-chlorodeoxyadenosine and to compare its activity with that of 9-beta-D-arabinofuranosyl-2-fluoroadenine, a related analog now in phase I/II clinical trials. The overall in vitro response rate (defined as less than 50% survival of tumor colony forming units) for 2-chlorodeoxyadenosine was: 8% and 23% at 1.0 and 10.0 micrograms/ml as a 1 hour pulse exposure, respectively; 11% and 31% at 1.0 and 10.0 micrograms/ml, as a continuous exposure, respectively. 2-Chlorodeoxyadenosine and 9-beta-D-arabinofuranosyl-2-fluoroadenine did not have identical spectra of antitumor activities in vitro, suggesting that both may be worthy of further clinical trial.