RESUMEN
Thalassemia is identified as a prevalent disease in Malaysia, known to be one of the developing countries. Fourteen patients with confirmed cases of thalassemia were recruited from the Hematology Laboratory. The molecular genotypes of these patients were tested using the multiplex-ARMS and GAP-PCR methods. The samples were repeatedly investigated using the Devyser Thalassemia kit (Devyser, Sweden), a targeted NGS panel targeting the coding regions of hemoglobin genes, namely the HBA1, HBA2, and HBB genes, which were used in this study. There were many different genetic variants found in 14 unrelated cases. Out of all fourteen cases, NGS was able to determine an additional -50 G>A (HBB:c.-100G>A) that were not identified by the multiplex-ARMS method, including HBA2 mutations, namely CD 79 (HBA2:c.239C>G). Other than that, CD 142 (HBA2:c.427T>C) and another non-deletional alpha thalassemia and alpha triplication were also not picked up by the GAP-PCR methods. We illustrated a broad, targeted NGS-based test that proposes benefits rather than using traditional screening or basic molecular methods. The results of this study should be heeded, as this is the first report on the practicality of targeted NGS concerning the biological and phenotypic features of thalassemia, especially in a developing population. Discovering rare pathogenic thalassemia variants and additional secondary modifiers may facilitate precise diagnosis and better disease prevention.
RESUMEN
BACKGROUND Plasma cell leukemia (PCL) is an aggressive form of plasma cell neoplasm. We report the first case of primary PCL successfully treated with upfront novel agents consisting of Venetoclax and daratumumab in combination with intensive chemotherapy and allogeneic transplantation. CASE REPORT A 59-year-old woman presented with epistaxis, gum bleeding, and blurred vision. On examination, she appeared pale, with multiple petechiae and hepatomegaly. Fundoscopy revealed retinal hemorrhages. Laboratory investigations revealed bicytopenia and leukocytosis, with mild coagulopathy and hypofibrinogenemia. Elevated globulin and calcium levels were also observed. Serum protein electrophoresis demonstrated IgG lambda paraproteinemia, with a serum-free light chain kappa-to-lambda ratio of 0.074. A skeletal survey revealed the presence of lytic lesions. Bone marrow investigations confirmed the presence of lambda-light-chain-restricted clonal plasma cells. FISH detected t(11;14) and 17p13.1 deletion. Therefore, a final diagnosis of primary PCL was made. The patient received 1 cycle of bortezomib, cyclophosphamide, and dexamethasone (VCD) and 5 cycles of Venetoclax-VCD, followed by an unsuccessful stem cell mobilization. One cycle of daratumumab in combination with bortezomib, lenalidomide, and dexamethasone (VRD) was then given. The patient achieved complete remission. She underwent allogeneic stem cell transplantation of an HLA-matched sibling donor. Post-transplant marrow assessment showed disease remission and absence of t(11;14) and 17p deletions. She was administered pamidronate and lenalidomide maintenance. She remained clinically well with a good performance status and no active graft-versus-host disease 18 months after transplant. CONCLUSIONS The success of our patient in achieving complete remission has highlighted the efficacy and safety of this novel therapy in the front-line management of PCL.
