Does Post-Transplant Maintenance Therapy With Tyrosine Kinase Inhibitors Improve Outcomes of Patients With High-Risk Philadelphia Chromosome-Positive Leukemia?
The effect of post-transplant maintenance tyrosine kinase inhibitors (TKIs) on the outcomes of allogeneic hematopoietic stem cell transplantation in high-risk Philadelphia chromosome-positive (Ph(+)) leukemia remains unknown.



A retrospective analysis that included allograft recipients with accelerated phase and blast phase chronic myeloid leukemia or Ph(+) acute lymphoblastic leukemia who had received post-transplant maintenance TKI therapy from 2004 to 2014.



A total of 26 patients, 9 with accelerated phase/blast phase CML and 17 with Ph(+) acute lymphoblastic leukemia, received maintenance post-transplant therapy with imatinib, dasatinib, nilotinib, or ponatinib. The TKI was selected according to the pretransplantation TKI response, anticipated toxicities, and ABL1 domain mutations, when present. Newer generation TKIs were initiated at a ≥ 50% dose reduction from the standard pretransplantation dosing to limit the toxicities and avoid therapy interruptions. TKIs were started a median of 100 days (range, 28-238 days) after transplantation and were administered for a median of 16 months (range, 8 days to 105 months). Eight patients discontinued therapy because of adverse events. With a median follow-up of 3.6 years (range, 4 months to 8.7 years), the 5-year relapse-free survival rate was 61%. All 3 patients who developed a relapse underwent successful salvage treatment and remained disease-free. The 5-year overall survival rate was 78%.



Maintenance TKI therapy after transplantation is feasible and might reduce the incidence of relapses and improve outcomes after allogeneic hematopoietic stem cell transplantation for patients with high-risk Ph(+) leukemia.
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Zachariah
Z
DeFilipp
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Amelia A
AA
Langston
Department of Biostatistics and Bioinformatics, Winship Cancer Institute of Emory University, Atlanta, GA.
Zhengjia
Z
Chen
Department of Biostatistics and Bioinformatics, Winship Cancer Institute of Emory University, Atlanta, GA.
Chao
C
Zhang
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Martha L
ML
Arellano
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Fuad
F
El Rassi
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Christopher R
CR
Flowers
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Vamsi K
VK
Kota
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Zaid
Z
Al-Kadhimi
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Rachel
R
Veldman
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Anand P
AP
Jillella
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Sagar
S
Lonial
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Edmund K
EK
Waller
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA. Electronic address: hkhoury@emory.edu.
Hanna J
HJ
Khoury
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000401:mortality / Q000628:therapy; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010677:Philadelphia Chromosome; D011182:Postoperative Care; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000401:mortality / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors
Acute lymphoblastic leukemia; Chronic myeloid leukemia; Ph(+); Relapse; TKIs