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Long-Term Survival of Patients with Chronic Phase Chronic Myeloid Leukemia Who Received Autologous Stem Cell Transplantation and Further Exposed to Tyrosine Kinase Inhibitors. a Study on Behalf of the French Society of Blood and Marrow Transplantation and the French Group of CML

Mauricette Michallet, Mohamad Sobh, Aude Charbonnier, Eric Deconinck, Viviane Dubruille, Valerie Coiteux, Martine Delain, Francoise Huguet, Delphine Rea, Dominique Bron, Nicole Raus, Alain Jacques Delmer, Pascal Lenain, Noel Milpied, Francois-Xavier Mahon, Franck Emmanuel Nicolini and Gabriel Etienne

Abstract

Background: Prior to the introduction of tyrosine kinase inhibitors (TKI), the median survival of chronic phase chronic myeloid leukemia (CP-CML) patients was approximately 60 months [Roy L et al, Blood 2006] and the standard treatment with interferon-alpha resulted in complete cytogenetic responses in about 30% of the patients [Bonifazi F. et al, Blood 2001]. Peripheral blood autologous stem cell transplantation (Auto-SCT) was first attempted for patients in transformation in order to restore a second CP and was introduced secondarily in CP to try to prolong the response. The principal rationale for autografting in CP resides on the reduction of the tumor burden and the number of leukemic cells at risk of developing blastic transformation, and the possibility of eradicating already mutated cells. In addition, it takes advantage as well of the endogenous mobilization in the circulation of Ph- HSCs. Nevertheless, Auto-SCT alone was not able to maintain a long-term cytogenetic and/or molecular remission. Nowadays, TKIs represent the state-of-the-art therapy for CML and the concept of Auto-SCT has only little interest while long-term follow-up and outcome in this setting are currently unknown.

Aims: The aim of our study is to evaluate the long-term outcome of CP-CML patients who received Auto-SCT and who have received TKIs later during their treatment course.

Patients: A total of 182 patients were included in this study, 114 (63%) were males and 68 (37%) females. The median age at diagnosis was 45 years (range: 20-66), interferon-alpha was initiated and then all patients received Auto-SCT between years 1989 and 2004 while they remained in CP, 30% of these patients were included in the auto-CML trials and the rest were treated accordingly. The median time between diagnosis and Auto-SCT was 24 months (range: 1-113). Stem cells source was peripheral blood in 172 (95%) of patients, mostly collected at diagnosis, and bone marrow in 10 (5%) patients. Patients were conditioned by Busulfan 4mg/Kg/day 4 days + Melphalan 140 mg/m2 1 day prior to the cells reinfusion. TKIs were introduced later on in these patients, information concerning the context of their use as well as response after treatment is currently under collection from centers and will be reported later during the meeting.

Results: After a median follow-up of 14.5 years (range: 2-30), the probability of overall survival (OS) for the whole population from diagnosis at 10, 15 and 20 years is 97% (95% CI: 92-99), 82% (95% CI: 74-88) and 68% (95% CI: 56-77). OS from date of Auto-SCT at 10, 15 and 20 years was 90% (95%CI: 83-94), 78% (95% CI: 69-85) and 63% (95%CI: 51-74) respectively. When we stratify the population according to age at Auto-SCT, patients younger than 45 years had an OS from diagnosis at 10, 15 and 20 years of 100%, 96% and 86% respectively compared to 94%, 72% and 54% respectively for those with 45 years and older, p=0.0015. A total of 33 (18%) patients died, 15 (8%) of them because of disease progression, 2 secondary malignancies, and the rest because of other causes including pneumonia, hemorrhage, renal failure and cirrhosis.

Additional data requests have been sent to centers querying about prognosis, molecular responses, treatment and disease details. An extensive analysis will be performed and the study will be updated with more results.

Conclusion: We demonstrate here with the preliminary results that Auto-SCT followed by TKIs has induced remarkable rates of long-term survival and raise the question about the place of intensification in the therapeutic strategy in CML.

Disclosures Charbonnier: Incyte: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Coiteux: BMS: Speakers Bureau; Incyte: Speakers Bureau. Rea: Novartis: Consultancy, Honoraria; Incyte: Honoraria; BMS: Consultancy, Honoraria; Pfizer: Honoraria. Delmer: Roche: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Honoraria; Abbvie: Consultancy, Honoraria. Mahon: PFIZER: Consultancy, Honoraria; BMS: Consultancy, Honoraria; NOVARTIS PHARMA: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; INCYTE: Honoraria. Nicolini: Incyte Biosciences: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; ARIAD: Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau. Etienne: BMS: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Consultancy, Research Funding.

  • * Asterisk with author names denotes non-ASH members.