Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in the Imatinib-Era: High Survival Rate Following Allogeneic HSCT after Imatinib Failure: Results of the German CML Study IV

Media type: E-Article

Title: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in the Imatinib-Era: High Survival Rate Following Allogeneic HSCT after Imatinib Failure: Results of the German CML Study IV

Contributor: Saussele, Susanne; Lauseker, Michael; Gratwohl, Alois; Heim, Dominik; Beelen, Dietrich Wilhelm; Döhner, Hartmut; Schwerdtfeger, Rainer; Ho, Anthony D.; Kolb, Hans-Jochem; Pfirrmann, Markus; Müller, Martin C.; Leitner, Armin; Proetel, Ulrike; Kovalevskaya, Elena; Haferlach, Claudia; Schlegelberger, Brigitte; Hasford, Joerg; Hochhaus, Andreas; Hehlmann, Ruediger

imprint: American Society of Hematology, 2008

Language: English

DOI: 10.1182/blood.v112.11.448.448

ISSN: 0006-4971; 1528-0020

Keywords: Cell Biology ; Hematology ; Immunology ; Biochemistry

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Footnote:

Description: Abstract Allogeneic HSCT remains an important option for patients with chronic myeloid leukemia (CML) who failed imatinib. Focus has been on second line tyrosine kinase inhibitors (TKI). Little is known on the outcome of HSCT for such patients. In July 2002, the German CML-Study Group activated a prospective randomized trial comparing different imatinib based strategies in chronic phase CML (CP). Elective early HSCT was considered for patients (pts) with EBMT score 0–1 for those with high disease risk, and after imatinib failure. By the end of July 2008, 1197 pts were randomized. In 80 (6,5 %) pts HSCT was documented. 52 pts were male (65%), 23 were high risk pts (28%) according to the Euro score. Median age at diagnosis was 37 years (yrs) (range 16–62), median time to HSCT was 12.6 months (mo, range 3.5–54 mo). EBMT score was 0–1 in 8 (10%), 2 in 10 (12%), 3–4 in 44 (55%) and 5 in 18 pts (23%). Median follow-up after HSCT was 19 mo (range 0–59). Cumulative response rates prior to HSCT were 68% for complete hematologic response, 23% for complete cytogenetic responses, and 9% for major molecular responses. Based on the indication for HSCT three groups were defined: early HSCT (n= 19, 23%; low EBMT score (n=9), high risk pts (n=7), patient request (n=3); HSCT after imatinib failure or intolerance in first CP (n=34, 43%) and HSCT in second CP or higher, accelerated phase or blast crisis (n=27, 34%). 14 pts died, 10 deaths were transplantation related, 4 CML related. Two pts with a molecular relapse were successfully treated with donor lymphocyte infusion in combination with TKI. Overall survival rate at two yrs for group one was 87.8%, for group two 93.8%, and for group three 49.5%. By EBMT score, survival rates were 100% for risk score 0–2, 82.2% for risk score 3–4, and 43.5% for risk score 5. Data from this prospective controlled cohort study clearly show that HSCT remains an attractive and important rescue therapy for CML patients with imatinib failure or intolerance, particularly for those with a low EBMT risk score. HSCT in 1st CP early HSCT HSCT for failure and intolerance in 1st CP Total HSCT in advanced phases N 19 34 53 27 Euro score high 6 8 14 9 intermediate 3 12 15 7 low 10 14 24 11 % male 63 56 60 78 Median age (range) 35 (16–56) 38 (21–56) 37 (16–56) 37 (18–62) Median time to HSCT (Range) (months) 8.5 (4.8–23.6) 17,5 (5.0– 53.7) 12.6 (4.8 53.7) 12.0 (3.5–54.1) EBMT score 0–1 5 3 8 0 2 5 4 9 1 3–4 9 26 35 9 &gt;=5 0 1 1 17 Best response CHR 11/18 28/34 39/52 14/26 CCyR 3/17 10/33 13/50 4/22 MMR 2/17 3/31 5/48 2/19 Response at HSCT BC 0 0 0 24 AP 0 0 0 3 CP 19 34 53 0 HR 11 19 30 0 Ccyr 2 2 4 0 MMR 0 0 0 0 Transplant source Sibling 10 10 20 9 Unrelated 9 24 33 18 Conditioning therapy standard 14 21 35 17 reduced 3 6 9 4 other 2 7 9 6 Source PB 13 26 39 22 BM 6 8 14 5 Dead 2 2 4 10 TRM 2 2 4 6 CML 0 0 0 4 Probability of survival at 2 years after HSCT 87.8% 93.8% 91.4% 49.5%

Access State: Open Access

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