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Introduction: Minimal residual disease (MRD) assessment in acute myeloid leukemia (AML) cases is a complex, multi-modality process and, though much of its clinical implications at different points are extensively studied, it remains even now a challenging area. It is a disease the biology of which governs the modality of MRD assessment; in patients harboring specific molecular targets, high sensitivity techniques can be applied. On the other hand, relapse is considered as the leading cause of treatment failure in AML patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). Materials and methods: Since November 2018 until June 2020, 10 AML patients underwent matched unrelated donor (MUD) HSCT at the University Clinic of Hematology-Skopje, Republic of North Macedonia. Molecular markers were identified in a total of 4 patients; 3 patients expressed chimeric fusion transcripts; two RUNX-RUNX1T1 and one for CBFB-MYH11. One patient harbored mutation in the transcription factor CCAAT/enhancer binding protein α (CEBPA). Post-transplant MRD kinetics was evaluated by using quantitative polymerase chain reaction (RT-qPCR) or multiplex fluorescent-PCR every three months during the first two years after the transplantation. Results: MRD negativity was achieved in three pre-transplant MRD positive patients by the sixth month of HSCT. They sustained hematological and molecular remission for 19, 9 and 7 months, respectively. The fourth patient died due to transplant-related complications. Conclusion: According to our experience, when molecularly-defined AML patients undergo HSCT, regular MRD monitoring helps predict impending relapse and direct future treatment strategies.

Posterior reversible encephalopathy syndrome (PRES) is one of the most serious complication after allogeneic stem cell transplantation in paediatric setting. It is most commonly reported as adverse event of immunosuppressive strategies during transplantation. We present a case of a 7 years old girl with myelodysplastic syndrome (MDS) treated with allogeneic stem cell transplantation (ASCT) at our department. Diagnosis of PRES was confirmed by imaging techniques during the first month after transplant and it was very likely connected with cyclosporine neurotoxicity. The aim of this article is to present our first experience in diagnosing and treating PRES in paediatric stem cell transplantation. Our experience showed that PRES is one of the reasons for higher transplant related mortality in children. Early prediction of factors contributing to PRES and closely monitoring of patient’s vital signs, especially blood pressure, neurological status and vision are the main contributors for challenging the patient with another immunosuppressive agent that has less neurological toxicity. Still studies have to be initiated to confirm the influence of PRES on transplant outcome.

Herein synchronous occurrence of Hodgkin lymphoma and secondary myelodysplastic syndrome in a 60 year old male patient with small cell lung cancer treated with combined chemotherapy (carboplatin and paclitaxel) and radiotherapy is presented. The objective of this report is to stress the importance of documenting and monitoring adverse drug reactions that arise from chemotherapy. After four years of treatment with the combined chemotherapy, the patient presented inguinal lymphadenopathy and enlarged lymph nodes and histopathology rapport was suggestive for plasmacytoid variant of Castleman disease. Three years later, biopsy of lymph node was performed and diagnosis of Hodgkin lymphoma – mixed cellularity has been established. Molecular analyses revealed presence of dominant monoclonal population of the immunoglobulin genes in the oligo/monoclonal background. Bone marrow biopsy findings suggested secondary myelodysplasia and revealed signs of hematopoietic cells dismaturation with signs of megaloblastic maturation of the erytropoetic lineage, appearance of ALIP (abnormal localization of immature precursors) in the myeloid lineage and dysplastic megakaryocytes. In addition, an increased level of polyclonal plasmacytes (lambda vs kappa was 60%:40%) was found. Hodgkin lymphoma and MDS occurring after 4 years of carboplatin/paclitaxel therapy might be contributed to the accumulation of alkylator-related DNA damage. This emphasize the need of outlining a monitoring plan regarding development of secondary leukemia and other malignant hematological proliferations should be outlined in the protocols.

Recently, V617F mutation in JAK2 tyrosine kinase gene was established as a marker of myeloproliferation, useful for proving clonality and securing diagnosis in a considerable proportion of the myeloproliferative neoplasms (MPN) The discovery presents a major breakthrough in the understanding of the pathogenesis of the MPN. Moreover, some studies suggest a possible role of the JAK2V617F mutation in the pathogenesis of some specific acute myeloid leukemia (AML) subtypes. To further improve the understanding of the role of JAK2V617F mutations in the pathogenesis and the clinical course of the myeloid malignancies we screened 192 patients with various MPN and AML for the mutations and analyzed the possible association between JAK2V617F mutations and the clinical features of MPNs patients. The frequency of V617F JAK2 mutation was analyzed by theallele-specific PCR assay. Out of 153 cases with known or suspected diagnoses of MPNs, 100 (65.3%) were positive for the JAK2V617F mutation and 53 (34.7%) were negative. In 39 AML cases the mutant allele V617F was not expressed. Correlations of the clinical features at diagnosis and long-term prognosis between the two JAK2-V617F different MPNs groups revealed comparability regarding all tested parameters except for the incidence of thrombotic history. Patients with the mutation had significantly higher incidence of thrombotic complication (38.5%), compared to the group without the mutation (19.2%) (P0.005). Our results confirmed the diagnostic significance of JAK2V617F mutation in MPNs and supported the notion that patients with the mutation should be classified in a new entity of MPNs.