Efficacy of combining dasatinib and FLAG-IDA for patients with chronic myeloid leukemia in blastic transformation

Abstract

using the HbA2 value of 3.4% as cut off. 8 Using the value of 30 mg/L for serum ferritin as cut off, 861 samples showed iron deficiency (ID) (group A) and 271 were without ID (group B) (Figure 1). The mean HbA2 value was 2.8%±0.79 in group A and 3.50%±1.23 in group B, with a significant difference (P=0.00001) among between the two groups. The distribution of the 253 samples with molecular analysis between groups A and B showed that 170 samples were part of group A and 83 of group B (Figure 1). From 170 samples of group A, 21 resulted positive for a b-globin gene mutation with a mean of HbA2 value of 4.90%±1.29. From 83 samples of group B, 29 resulted positive for a b-mutation (mean of HbA2 value: 5.37%±0.87). The comparison between the HbA2 mean value of b-thalassemia carriers with (group A) or without (group B) ID, using the value of 30 mg/L as serum ferritin cut off, does not show a significant difference (P=0.060) and in both groups HbA2 levels are more than 3.4%. Reduction of HbA2 has been reported to be linked to the severity of anemia 9 so that it is possible that the value of 30 mg/L for serum ferritin defines an ID not sufficiently severe or not sufficiently prolonged to significantly reduce the level of HbA2. The ROC analysis, performed with samples of group A, at the 3.4% HbA2 cutoff value, showed sensitivity and specificity of 74.19% and 95.8%, respectively. The false negative samples were 8 of 30 (26,6%): 3 presented Hb b variants, co-eluting with HbA, (Hb Valletta, Hb Ernz and Hb City of Hope) that do not require prenatal diagnosis, one showed an undefined single nucleotide polymorphism (SNP) in the b-globin gene of ambiguous diagnostic significance, 8 2 samples presented, respectively, the α-globin gene triplication (ααα anti3.7), and the b-globin gene promoter mutation,-101 (HBB c.-151C→T), and finally, 2 samples showed co-heredity of b + and d + mutation. The samples with ααα anti3.7 and the-101 beta mutation showed, respectively, HbA2 values of 3.0% and 3.2% with a lower value of Hb (<12 g/dL) and MCV (<75 fL). The contemporary analysis of hematologic and hemoglobin data enable us to identify these subjects as samples that must be submitted to molecular analysis if their partners are carriers of b thalassemia. 6 While, in other cases, it is recommended to remeasure HbA2 after ID treatment. In the 2 samples showing co-heredity of b + and d + mutation, the large reduction is principally associated with the presence of delta mutation rather than serum ferritin value. Our results show that the presence of iron deficiency did not preclude the detection of classical b carrier in our population. There could be some problems in the presence of silent b mutation or α gene triplication with ID, because HbA2 shows almost normal levels. However, the reduction in total Hb and MCV, and possible persistently low MCV and MCH after iron suppletion, should suggest greater attention is needed and molecular analysis exploring both the α and the b genes should be carried out, especially if the subject is a partner of...

Very long survival in complete cytogenetic remission in an adolescent with lymphoid blast crisis of chronic myeloid leukemia after treatment with intensive ALL‐directed chemotherapy combined with continuous imatinib

“…In small series, this approach was shown to be highly efficacious, with unprecedented CR rates and a high probability of achieving CGR and major MRs. In accordance with expectations, the quality of MRs and length of survival were both higher in imatinib‐naïve patients . However, all cases of “cure” were observed after allogeneic HCT.…”

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European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

“…Patients returning to a second CP (CP2) before allo-SCT have improved transplantation outcomes [97,98]. The addition of a TKI to chemotherapy-based AML [99,100] or ALL regimens [101] improves the chance of achieving CP2. The choice of TKI should be based on prior therapies and BCR-ABL1 KD-mutational status.…”

Dasatinib combined with weekly administration of vincristine as effective therapy in sudden or resistant Ph+ lymphoid blast crisis of chronic myeloid leukaemia

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