ABSTRACT
Acquired resistance to tyrosine kinase inhibitors (TKIs) remains a therapeutic challenge in the treatment of chronic myeloid leukemia (CML). The most studied reason for TKI resistance is the acquisition of mutations within the BCR::ABL1 tyrosine kinase domain (KDM) and of which the majority of which occur at seven codons within this region. A case of CML is described in which presence of a rare D363G BCR::ABL1 KDM resulted in a suboptimal response to frontline imatinib. Switching to dasatinib resulted in achieving a sustained major molecular response that was maintained after a subsequent switch to bosutinib due to the side effects. Reporting of such cases is important for the future management of any CML patients with this rare mutation.
ABSTRACT
Posttransplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplant. We identified 40 patients diagnosed with PTLD between 2009 and 2020 and analyzed their presentation, treatment strategies, and outcomes. Median age at diagnosis was 52.5 years (range 21.3 to 79). Median duration of immunosuppression was 95 months (range 4 to 292). Diffuse large B cell lymphoma (n = 16, 40%) and Burkitt lymphoma (n = 6, 15%) were the most common histological subtypes. First-line therapy varied. The median number of treatment lines was 1 (range 0 to 4). Sixteen patients (40%) achieved complete response after first-line therapy. Nineteen patients (47.5%) relapsed or progressed and received salvage therapy; 45% were alive at the end of the study period (median survival 52 months; range 1 to 266; 95% confidence interval 0 to 104). Causes of death included lymphoma-related (45.5%), therapy-related (27.3%), and other (27.3%). Five (22.7%) died within 3 months of diagnosis. Pearson's r test identified disease stage (P = .045) and proliferation index (P = .005) as negative predictors of response to frontline therapy. Bone marrow involvement (P = .033) and increased age (P = .018) were significant predictors of survival. Early mortality and poor response to frontline therapy are common, outlining the need for improved treatment strategies.
Subject(s)
Lymphoproliferative Disorders/diagnosis , Organ Transplantation/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Postoperative Period , Risk Factors , Young AdultABSTRACT
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. The chromosomal abnormality t(14;18)(q32;q21) is most commonly associated with neoplasms of a follicular center cell origin. However, t(14;18) has also been reported in rare cases of CLL. OBJECTIVE: We describe the clinicopathologic, immunophenotypic, conventional, and molecular cytogenetic features of two rare cases proven to be CLL morphologically and immunologically in which t(14;18) was found as the sole cytogenetic abnormality. METHODS: Morphologic, flow cytometric analysis and molecular cytogenetic of peripheral blood and/or bone marrow samples were analyzed. RESULTS: Cytomorphologically, the cells were small mature lymphocytes without any findings that had characteristics of follicular lymphoma (FL) such as indented or clefted nuclei. Immunologic findings were characteristic of typical CLL without expression of CD10. A cytogenetic study revealed the two cases of CLL carrying t(14;18)(q32;q21). CONCLUSION: We concluded that CLL with t(14;18) is rare and should be differentiated from FL as the therapy is highly diverse between both diseases. Using immunoglobulin heavy chain gene (IGH) probes are important in the workup of patients with suspected CLL and suggest that the IGH probe should be used routinely in all CLL fluorescence in situ hybridization (FISH) panels.
ABSTRACT
The fms-like tyrosine kinase 3 (FLT3) gene is a member of the class III receptor tyrosine kinase family. Mutations of FLT3 were first described in 1997 and account for the most frequent molecular mutations in acute myeloid leukemia. Currently, there is no published data on FLT3 mutations in Saudi acute lymphoblastic leukemia (ALL) patients. In this retrospective study, we have examined a cohort of 77 ALL patients to determine the prevalence of FLT3 mutations and the possible prognostic relevance of these mutations in ALL patients. Correlations to other biologic factors such as karyotype, molecular mutations, and leukocyte count were also considered. FLT3 internal tandem duplication (ITD) mutations and point mutation in tyrosine kinase domain (D835) were analyzed in ALL patients, at diagnosis, by polymerase chain reaction (PCR). Two cases (2.6%, 2/77) were positive for FLT3 mutations; one was found to have FLT3/ITD and the other FLT3/D835. Our findings suggest that FLT3 mutations are not common in Saudi ALL and do not affect clinical outcome.
ABSTRACT
The Fms-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase that plays a key role in cell survival, proliferation, and differentiation of hematopoietic stem cells. Mutations of FLT3 were first described in 1997 and account for the most frequent molecular mutations in acute myeloid leukemia (AML). AML patients with FLT3 internal tandem duplication (ITD) mutations have poor cure rates the prognostic significance of point mutations; tyrosine kinase domain (TKD) is still unclear. We analyzed the frequency of FLT3 mutations (ITD and D835) in patients with AML at diagnosis; no sufficient data currently exist regarding FLT3 mutations in Saudi AML patients. This study was aimed at evaluating the frequency of FLT3 mutations in patients with AML and its significance for prognosis. The frequency of FLT3 mutations in our study (18.56%) was lower than many of the reported studies, FLT3-ITD mutations were observed in 14.4%, and FLT3-TKD in 4.1%, of 97 newly diagnosed AML patients (82 adult and 15 pediatric). Our data show significant increase of FLT3 mutations in male more than female (13 male, 5 female). Our results support the view that FLT3-ITD mutation has strong prognostic factor in AML patients and is associated with high rate of relapse, and high leucocytes and blast count at diagnosis and relapse.
