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Fludarabine with cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with poor-risk chronic lymphocytic leukemia

Fludarabine with cytarabine followed by reduced-intensity conditioning and allogeneic... Allogeneic stem cell transplantation (SCT) is a treatment option for patients with poor-risk chronic lymphocytic leukemia (CLL). Sequential use of chemotherapy and reduced-intensity conditioning has been proposed to improve the treatment outcomes. Fludarabine (30 mg/m 2 /day) and cytarabine (2 g/m 2 /day) for 4 days (combination of fludarabine with cytarabine; FAraC) were used for cytoreduction. After 3 days of rest, reduced intensity conditioning (RIC) was carried out consisting of 4 Gy total body irradiation, 10–20 mg/kg/day antithymocyte globulin for 3 days, and 40–60 mg/kg/day cyclophosphamide for 2 days. The median time of neutrophil engraftment was 16 days. The most frequent toxicities were grades III/IV infections in 12 of 15 cases and gastrointestinal toxicities in 8 of 15 cases. Remission (complete remission + partial remission) was achieved in 14 of 15 patients (93 %), minimal residual disease negativity according to flowcytometric analysis was observed in 10 patients. Nonrelapse mortality after 1 and 2 years was 7 and 13 %, respectively. After the median follow-up from SCT of 30 months, 80 % of patients were alive (12/15), three patients have died, and three relapses occurred. The FAraC–RIC protocol seems to be a promising approach to the treatment of poor-risk CLL with a high response rate of 93 % and favorable progression-free survival and overall survival of 70 and 85 % at 2 years after SCT, respectively. Other prospective clinical trials are needed to confirm the results of this novel therapeutic strategy. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Hematology Springer Journals

Fludarabine with cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with poor-risk chronic lymphocytic leukemia

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Publisher
Springer Journals
Copyright
Copyright © 2013 by Springer-Verlag Berlin Heidelberg
Subject
Medicine & Public Health; Hematology; Oncology
ISSN
0939-5555
eISSN
1432-0584
DOI
10.1007/s00277-012-1579-y
pmid
23014659
Publisher site
See Article on Publisher Site

Abstract

Allogeneic stem cell transplantation (SCT) is a treatment option for patients with poor-risk chronic lymphocytic leukemia (CLL). Sequential use of chemotherapy and reduced-intensity conditioning has been proposed to improve the treatment outcomes. Fludarabine (30 mg/m 2 /day) and cytarabine (2 g/m 2 /day) for 4 days (combination of fludarabine with cytarabine; FAraC) were used for cytoreduction. After 3 days of rest, reduced intensity conditioning (RIC) was carried out consisting of 4 Gy total body irradiation, 10–20 mg/kg/day antithymocyte globulin for 3 days, and 40–60 mg/kg/day cyclophosphamide for 2 days. The median time of neutrophil engraftment was 16 days. The most frequent toxicities were grades III/IV infections in 12 of 15 cases and gastrointestinal toxicities in 8 of 15 cases. Remission (complete remission + partial remission) was achieved in 14 of 15 patients (93 %), minimal residual disease negativity according to flowcytometric analysis was observed in 10 patients. Nonrelapse mortality after 1 and 2 years was 7 and 13 %, respectively. After the median follow-up from SCT of 30 months, 80 % of patients were alive (12/15), three patients have died, and three relapses occurred. The FAraC–RIC protocol seems to be a promising approach to the treatment of poor-risk CLL with a high response rate of 93 % and favorable progression-free survival and overall survival of 70 and 85 % at 2 years after SCT, respectively. Other prospective clinical trials are needed to confirm the results of this novel therapeutic strategy.

Journal

Annals of Hematology – Springer Journals

Published: Jan 1, 2013

References

  • Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009
    Ljungman, P; Bregni, M; Brune, M; Cornelissen, J; Witte, T; Dini, G
  • Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus
    Dreger, P; Corradini, P; Kimby, E; Michallet, M; Miligan, D; Schetelig, J
  • Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German Study Group CLL3X trial
    Dreger, P; Dohner, H; Ritgen, M; Bottcher, S; Busch, R; Dietrich, S
  • Modern and conventional prognostic markers of chronic lymphocytix leukaemia in the everyday haematological practice
    Doubek, M; Mayer, J; Obrtlikova, P; Smolej, L; Cmunt, E; Schvarz, J
  • The effect of allogeneic stem cell transplantation on high risk chronic lymphocytic leukaemia: a single centre retrospective analysis
    Valkova, V; Schwarz, J; Vitek, A; Markova, M; Polhreich, D; Benesova, K
  • Graft-versus-leukaemia effect after non-myeloablative haematopoetic transplantation can overcome the unfavourable expression of ZAP-70 in refractory chronic lymphocytic leukaemia
    Khouri, IF; Saliba, RM; Admirand, J
  • Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning
    Sorror, ML; Storer, BE; Sandmaier, BM
  • Predictors of improved progression-free survival after nonmyeloablativne allogeneic stem cell transplantation for advanced chronic lymphocytic leukemia
    Brown, JR; Kim, HT; Li, S
  • Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome
    Schmid, C; Schleuning, M; Ledderose, G
  • Efficacy and toxicity of the FLAMSA/RIC regimen in 40 patients with high-risk AML: a single centre experience
    Krejci, M; Brychtova, Y; Doubek, M; Toskova, M; Racil, Z; Koristek, Z
  • Fludarabine infusion potentiates arabinosylcytosine metabolism in lymphocytes of patients with chronic lymphocytic leukemia
    Gandhi, V; Kemera, A; Keating, MJ; Plunket, W
  • Phase I–II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patiens with Richter’s syndrome or fludarabine-refractory chronic lymphocytic leukemia
    Tsimberidou, AM; Wierda, WG; Plunkett, W
  • Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the Infectious Disease Working Party (AGIHO) of the German Society of Haematology and Oncology
    Krüger, WH; Bohlius, J; Cornely, OA; Einsele, H; Hebart, H; Massenkeil, G
  • Consensus conference on acute GVHD grading
    Przepiorka, D; Weisdorf, D; Martin, P
  • Chronic graft-versus-host syndrome in man. A long-term clinicopatologic study of 20 Seattle patients
    Shulman, HM; Sullivan, KM; Weiden, PL
  • Gudelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on chronic lymphocytic leukemia updating the National Cancer Institute-Working Group 1996 guidelines
    Hallek, M; Cheson, BD; Catovsky, D
  • Quantitative MRD monitoring identifies distinct GVL response patterns after allogeneic stem cell transplantation for chronic lymphocytic leukemia: results from the GCLLSG CLL3X trial
    Ritgen, M; Böttcher, S; Stilgenbauer, S
  • Summary: reports on quantitative analysis of chimerim after allogeneic stem cell transplantation by PCR amplification of microsatellite markers and capillary electrophoresis with fluorescence detection
    Lion, T
  • Increasing hematopoietic microchimerism is a reliable indicator of incipient AML relapse
    Horky, O; Mayer, J; Kablaskova, L; Razga, F; Krejci, M; Kissova, J
  • International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia
    Rawstron, AC; Villamor, N; Ritgen, M
  • Fludarabine, amsacrine, high-dose cytarabine and 12 Gy total body irradiation followed by allogeneic hematopoietic stem cell transplantation is effective in patients with relapsed or high-risk acute lymphoblastic leukemia
    Zohren, F; Czibere, A; Bruns, I
  • Results of alemtuzumab-based reduced intensity allogeneic transplantation for chronic lymphocytic leukemia: a British Society of Blood and Marrow Transplantation study
    Delgado, J; Thomson, K; Russel, N
  • Allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: ready for primetime?
    Delgado, J; Miligan, DW; Dreger, P
  • Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation
    Schmidt, C; Schleuning, M; Schwerdtfeger, R
  • Nonmyeloablative allogeneic stem cell transplantation (NST) after truly nonmyeloablative and reduced intensity conditioning regimens
    Banna, GL; Aversa, S; Sileni, VC; Favaretto, A; Ghiotto, C
  • Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomized, open-label, multicentre phase 3 trial
    Finke, J; Bethge, WA; Schmoor, C
  • Reduced-intensity conditioning lowers treatment-relapted mortality of allogeneic stem cell transplantation for chronic lymphocytic leukemia: a population-matched analysis
    Dreger, P; Brand, R; Milligan, D
  • Qualitative and quantitative polymerase chain reaction monitoring of minimal residual duseiase in relaposed chronic lymphocytic leukemia: early assesment can predict long-term outcome after reduced intensity allogeneic transplantation
    Farina, L; Carniti, C; Doredo, A
  • Clinical significance of minimal residual disease, as assessed by different techniques, after stem cell transplantation for chronic lymphocytic leukemia
    Moreno, C; Villamor, N; Esteve, J