Melphalan and purine analog-containing preparative regimens

Reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation

Sergio Giralt, Peter F. Thall, Issa Khouri, Xuemei Wang, Ira Braunschweig, Cindy Ippolitti, David Claxton, Michele Donato, Jill Bruton, Agueda Cohen, Marilyn Davis, Borje S. Andersson, Paolo Anderlini, James Gajewski, Steven Kornblau, Michael Andreeff, Donna Przepiorka, Naoto T. Ueno, Jeff Molldrem, Richard Champlin

Research output: Contribution to journalArticle

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Abstract

A reduced-intensity preparative regimen consisting of melphalan and a purine analog was evaluated for allogeneic transplantation in 86 patients who had a variety of hematologic malignancies and were considered poor Candidates for conventional myeloablative therapies because of age or comorbidity. Seventy-eight patients received fludarabine 25 mg/m2 daily for 5 days in combination with melphalan 180 mg/m2 (n = 66) or 140 mg/m2 (n = 12). Eight patients received cladribine 12 mg/m2 continuous infusion for 5 days with melphalan 180 mg/m2. The median age was 52 years (range, 22-70 years). Disease status at transplantation was either first remission or first chronic phase in 7 patients, untreated first relapse or subsequent remission in 16 patients, and refractory leukemia or transformed chronic myelogenous leukemia in 63 patients. Non-relapse mortality rates on day 100 were 37.4% for the fludarabine/melphalan combination and 87.5% for the cladribine/melphalan combination. The median percentage of donor cells at 1 month in 75 patients was 100% (range, 0%-100%). The probability of grade 2-4 and 3-4 acute graft-versus-host disease was 0.49 (95% Cl, 0.38-0.60) and 0.29 (95% Cl, 0.18-0.41), respectively. Disease-free survival at 1 year was 57% for patients in first remission or chronic phase and 49% for patients with untreated first relapse or in a second or later remission. On multivariate analysis the strongest predictor for disease-free survival was a good or intermediate risk category. In summary, fludarabine/melphalan combinations are feasible in older patients with associated comorbidities, and long-term disease control cart be achieved with reduced-intensity conditioning in this population.

Original languageEnglish (US)
Pages (from-to)631-637
Number of pages7
JournalBlood
Volume97
Issue number3
DOIs
StatePublished - Feb 1 2001
Externally publishedYes

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Melphalan
Cell Transplantation
Hematologic Neoplasms
Stem Cells
Cladribine
Disease control
Disease-Free Survival
Comorbidity
Grafts
Refractory materials
purine
Recurrence
Homologous Transplantation
Graft vs Host Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Multivariate Analysis
Transplantation
fludarabine
Tissue Donors

ASJC Scopus subject areas

  • Hematology

Cite this

Melphalan and purine analog-containing preparative regimens : Reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. / Giralt, Sergio; Thall, Peter F.; Khouri, Issa; Wang, Xuemei; Braunschweig, Ira; Ippolitti, Cindy; Claxton, David; Donato, Michele; Bruton, Jill; Cohen, Agueda; Davis, Marilyn; Andersson, Borje S.; Anderlini, Paolo; Gajewski, James; Kornblau, Steven; Andreeff, Michael; Przepiorka, Donna; Ueno, Naoto T.; Molldrem, Jeff; Champlin, Richard.

In: Blood, Vol. 97, No. 3, 01.02.2001, p. 631-637.

Research output: Contribution to journalArticle

Giralt, S, Thall, PF, Khouri, I, Wang, X, Braunschweig, I, Ippolitti, C, Claxton, D, Donato, M, Bruton, J, Cohen, A, Davis, M, Andersson, BS, Anderlini, P, Gajewski, J, Kornblau, S, Andreeff, M, Przepiorka, D, Ueno, NT, Molldrem, J & Champlin, R 2001, 'Melphalan and purine analog-containing preparative regimens: Reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation', Blood, vol. 97, no. 3, pp. 631-637. https://doi.org/10.1182/blood.V97.3.631
Giralt, Sergio ; Thall, Peter F. ; Khouri, Issa ; Wang, Xuemei ; Braunschweig, Ira ; Ippolitti, Cindy ; Claxton, David ; Donato, Michele ; Bruton, Jill ; Cohen, Agueda ; Davis, Marilyn ; Andersson, Borje S. ; Anderlini, Paolo ; Gajewski, James ; Kornblau, Steven ; Andreeff, Michael ; Przepiorka, Donna ; Ueno, Naoto T. ; Molldrem, Jeff ; Champlin, Richard. / Melphalan and purine analog-containing preparative regimens : Reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. In: Blood. 2001 ; Vol. 97, No. 3. pp. 631-637.
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abstract = "A reduced-intensity preparative regimen consisting of melphalan and a purine analog was evaluated for allogeneic transplantation in 86 patients who had a variety of hematologic malignancies and were considered poor Candidates for conventional myeloablative therapies because of age or comorbidity. Seventy-eight patients received fludarabine 25 mg/m2 daily for 5 days in combination with melphalan 180 mg/m2 (n = 66) or 140 mg/m2 (n = 12). Eight patients received cladribine 12 mg/m2 continuous infusion for 5 days with melphalan 180 mg/m2. The median age was 52 years (range, 22-70 years). Disease status at transplantation was either first remission or first chronic phase in 7 patients, untreated first relapse or subsequent remission in 16 patients, and refractory leukemia or transformed chronic myelogenous leukemia in 63 patients. Non-relapse mortality rates on day 100 were 37.4{\%} for the fludarabine/melphalan combination and 87.5{\%} for the cladribine/melphalan combination. The median percentage of donor cells at 1 month in 75 patients was 100{\%} (range, 0{\%}-100{\%}). The probability of grade 2-4 and 3-4 acute graft-versus-host disease was 0.49 (95{\%} Cl, 0.38-0.60) and 0.29 (95{\%} Cl, 0.18-0.41), respectively. Disease-free survival at 1 year was 57{\%} for patients in first remission or chronic phase and 49{\%} for patients with untreated first relapse or in a second or later remission. On multivariate analysis the strongest predictor for disease-free survival was a good or intermediate risk category. In summary, fludarabine/melphalan combinations are feasible in older patients with associated comorbidities, and long-term disease control cart be achieved with reduced-intensity conditioning in this population.",
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AU - Thall, Peter F.

AU - Khouri, Issa

AU - Wang, Xuemei

AU - Braunschweig, Ira

AU - Ippolitti, Cindy

AU - Claxton, David

AU - Donato, Michele

AU - Bruton, Jill

AU - Cohen, Agueda

AU - Davis, Marilyn

AU - Andersson, Borje S.

AU - Anderlini, Paolo

AU - Gajewski, James

AU - Kornblau, Steven

AU - Andreeff, Michael

AU - Przepiorka, Donna

AU - Ueno, Naoto T.

AU - Molldrem, Jeff

AU - Champlin, Richard

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N2 - A reduced-intensity preparative regimen consisting of melphalan and a purine analog was evaluated for allogeneic transplantation in 86 patients who had a variety of hematologic malignancies and were considered poor Candidates for conventional myeloablative therapies because of age or comorbidity. Seventy-eight patients received fludarabine 25 mg/m2 daily for 5 days in combination with melphalan 180 mg/m2 (n = 66) or 140 mg/m2 (n = 12). Eight patients received cladribine 12 mg/m2 continuous infusion for 5 days with melphalan 180 mg/m2. The median age was 52 years (range, 22-70 years). Disease status at transplantation was either first remission or first chronic phase in 7 patients, untreated first relapse or subsequent remission in 16 patients, and refractory leukemia or transformed chronic myelogenous leukemia in 63 patients. Non-relapse mortality rates on day 100 were 37.4% for the fludarabine/melphalan combination and 87.5% for the cladribine/melphalan combination. The median percentage of donor cells at 1 month in 75 patients was 100% (range, 0%-100%). The probability of grade 2-4 and 3-4 acute graft-versus-host disease was 0.49 (95% Cl, 0.38-0.60) and 0.29 (95% Cl, 0.18-0.41), respectively. Disease-free survival at 1 year was 57% for patients in first remission or chronic phase and 49% for patients with untreated first relapse or in a second or later remission. On multivariate analysis the strongest predictor for disease-free survival was a good or intermediate risk category. In summary, fludarabine/melphalan combinations are feasible in older patients with associated comorbidities, and long-term disease control cart be achieved with reduced-intensity conditioning in this population.

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