Two months from the initiation of dasatinib abnormal FDG

Two months from the initiation of dasatinib, abnormal FDG uptake of the left femur tumor had disappeared. Examination of peripheral blood and the bone marrow examination showed that a complete cytogenetic response was achieved and a ratio of BCR-ABL to ABL on the international scale was 0.21%. Her disease was well controlled with dasatinib. However, we considered that prompt allogeneic hematopoietic stem cell transplantation (allo-HSCT) was necessary for long-term remission. Although she did not have a sibling donor with identical human leukocyte (-)-JQ1 (HLAs), her mother was HLA-1 allele-mismatched for the graft-versus-host direction. Therefore, we performed allo-HSCT from her mother 4 months after the diagnosis. She achieved a complete molecular response with sensitivity of 4.5-log 1 month after transplantation, and the osteolytic region at the greater trochanter of the left femur gradually ossified. Considering the high prevalence of relapse, dasatinib maintenance was started on the 120th day after transplantation. The dose was reduced to 20mg once daily, but she could not tolerate dasatinib (grade-2 malaise and grade-3 maculopapular rash). She has been in complete remission without the need for a tyrosine kinase inhibitor (TKI) for two and a half years after transplantation, with excellent performance status.
Patients with high risk myelodysplasia (HR-MDS) and acute myeloid leukaemia (AML) with chromosomal changes involving deletion of the long arm of chromosome 5 (del5q), especially with complex karyotype, rarely have a durable response to combination chemotherapy. In the subgroup with monosomal karyotype there are no long term survivors . Recent experience indicates that the incidence of del5q in AML is ~20–30%, with only 20–25% of patients achieving complete remission (CR) . Additionally, therapy has significant toxicity, with induction death rates ~20% even in younger patients . Conversely, patients with low risk MDS and del5q can respond dramatically to lenalidomide at conventional doses . Thus, studies have investigated lenalidomide therapy in AML/HR-MDS. A phase 2 study of lenalidomide in HR- MDS with the del5q abnormality (alone or with other cytogenetic abnormalities) indicated a 20% CR rate with lenalidomide 10mg once a day, escalated to 15mg in suboptimally responding patients. However, all responders had isolated del5q . Subsequent studies have evaluated escalating doses up to 50mg daily but response rates remained ~4% . A phase 1 study in relapsed/refractory AML patients also indicated that lenalidomide can be tolerated up to 50mg daily, but there were no CR\'s in the del5q population. Those that did respond had low presenting white cell counts suggesting limited efficacy as monotherapy in proliferative disease Additionally, the Nordic group had similar findings when they assessed lenalidomide monotherapy up to 20mg daily in a phase 2 study for MDS/AML patients with any form of chromosome 5 abnormality and noted no response in patients with TP53 mutation . More recently a phase 1 study of sequential therapy with azacitidine and lenalidomide has identified an alternative approach capable of inducing haematological improvement and complete cytogenetic remissions, although has significant haematological toxicity .
Case report A 56-year-old male was admitted to our Hospital in October 2010 because of asthenia, slight fever, and weight loss. Blood examination revealed hemoglobin 7.5g/dL, platelet count 495,000/uL, white blood cell count 335,000/uL with neutrophils 80%, basophils 10%, myelocytes 6%, and promyelocytes 3%. Lactate dehydrogenase was 1440U/L. Physical examination revealed splenomegaly. Bone marrow (BM) aspirate showed myeloid hyperplasia. The hematological picture was indicative of accelerated phase chronic myeloid leukemia (CML). Cytogenetic analysis showed the presence of a t(9;22)(q34;q11) in all examined metaphases (Fig. 1 upper). Fluorescent in situ hybridization (FISH) using the LSI BCR/ABL Dual-Color, Dual Fusion (D-FISH) (Abbott Molecular-Vysis, Des Plaines,IL) showed two fusions, one green and one orange signal (2F1G1O) confirming the presence of the BCR/ABL1 and ABL1/BCR fusion genes without deletions adjacent to the translocation junctions (Fig. 2A).