Hematopoietic stem cell transplantation for T315I-mutated chronic myelogenous leukemia.
BACKGROUND
The T315I mutation of BCR/ABL gene is known to produce complete resistance of chronic myelogenous leukemia (CML) to all currently available BCR/ABL inhibitors. The data suggesting poor median survival of these patients may indicate that they should be primary candidates for allogeneic stem cell transplantation (alloSCT). However, evidence on efficiency of this treatment modality in CML with T315I mutation is lacking.


METHODS
A 25-year-old patient was diagnosed with Philadelphia chromosome positive CML in accelerated phase. As he did not have an HLA-identical sibling or fully-matched unrelated bone marrow donor, treatment with low dose tyrosine kinase inhibitor - imatinib was initiated. Despite satisfactory hematological remission, he failed to achieve complete cytogenetic remission within the first year of treatment. Moreover, despite escalation of imatinib dosage, the disease relapsed after further 3 months of treatment. Molecular studies revealed T315I mutation of BCR/ABL gene. He responded poorly to interferon alpha (IFN-alpha) and we decided to perform alloSCT from a partially mismatched (8/10 HLA allele match) unrelated donor. The course of transplantation was complicated by staphylococcal sepsis, grade I skin acute GvHD and limited chronic skin GVHD. However, the goal of alloSCT was achieved and the patient remains in complete molecular remission at week +68 post-transplantation.


CONCLUSIONS
The clinical course of this case supports the idea that allogeneic hematopoietic transplantation is a viable treatment option for patients with CML bearing T315I mutation.
Basak
Grzegorz
G
Department of Hematology, Oncology and Internal Diseases, The Medical University of Warsaw, Poland. gbasak@ib.amwaw.edu.pl
Torosian
Tigran
T
Snarski
Emilian
E
Niesiobedzka
Joanna
J
Majewski
Miroslaw
M
Gronkowska
Anna
A
Urbanowska
Elzbieta
E
Jedrzejczak
Wieslaw
W
D000328:Adult; D019943:Amino Acid Substitution; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics; D016313:Genes, abl; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy*; D015465:Leukemia, Myeloid, Accelerated Phase / Q000188:drug therapy / Q000235:genetics / Q000628:therapy; D008297:Male; D020125:Mutation, Missense; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012074:Remission Induction; D014184:Transplantation, Homologous
D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl