The impact of additional cytogenetic abnormalities at diagnosis and during therapy with tyrosine kinase inhibitors in Chronic Myeloid Leukaemia.

BACKGROUND: Chronic Myeloid Leukemia's (CML) treatment was optimized since the development of tyrosine kinase inhibitors (TKI) and an increased overall survival during TKI was noticed. During the TKI era, protocols for assessing response and resistance to treatment were developed. Additional chromosomal abnormalities (ACAs) are strongly associated with disease progression but their prognostic impact and influence on treatment response are yet to be defined. The aim of this study was to analyze the impact of ACAs on time to achieve complete cytogenetic response (CCyR), treatment and overall survival. MATERIALS AND METHODS: Since 2005 until 2013, the data from the Hematology and Bone Marrow Transplantation Department of Fundeni Clinical Institute was collected. In this observational retrospective single centre study, 28 CML patients with ACAs at diagnosis and during TKI treatment were included. RESULTS: From ACAs at diagnosis group, the most frequent major route ACAs were trisomy 8, trisomy 19 and second Philadelphia (Ph) chromosome and the most frequent minor route ACAs were monosomies and structural abnormalities (inversions and translocations). From the ACAs during the TKI group, the most frequent major route cytogenetic abnormalities in Ph positive and negative cells were trisomy 8, trisomy 19 and second Ph chromosome and the most frequent minor route cytogenetic abnormalities in Ph positive and negative cells were marker chromosomes and structural abnormalities (inversions, translocations and dicentric chromosomes). CONCLUSIONS: In both groups, the time to CCyR was longer and long-term results were inferior in comparison with standard patients but the differences were not significant and in accordance to published data. The 12 months follow-up after the study's end showed that 26 patients were alive and in long-term CCyR and 2 deaths were reported. ABBREVIATIONS: CML = Chronic Myeloid Leukemia, BCR-ABL1 = Break Cluster Region - Abelson gene, TKI = tyrosine kinase inhibitor treatment, ACAs = additional cytogenetic abnormalities, CCyR = complete cytogenetic response, PCyR = partial cytogenetic response, mCyR = minor cytogenetic response, MMR = major molecular response, HSCT = hematopoietic stem cell transplant, HLA = human leukocyte antigens, CP = chronic phase, AP = accelerated phase, BP = blast phase, OS = overall survival, CBA = chromosome banding analysis, +8 = trisomy 8, i(17q) = isochromosome (17q), +Ph = second Philadelphia chromosome, -7 = monosomy 7, -17 = monosomy 17, +17 = trisomy 17, -21 = monosomy 21, +21 = trisomy 21, -Y = loss of Y chromosome, ELN = European LeukemiaNet, IMA600 = Imatinib 600 mg daily, IMA400 = Imatinib 400 mg daily, NILO600 = Nilotinib 600 mg daily, DASA100 = Dasatinib 100mg daily, DASA140 = Dasatinib 140 mg daily.

Mucormycosis during Imatinib treatment: case report.

UNLABELLED: Philadelphia chromosome positive acute lymphoblastic leukemia is classified as a very high-risk group and it requires an intensive chemotherapy regimen associated with tyrosine-kinase inhibitors and allogeneic hematopoietic stem cell transplant from related or unrelated HLA matched donor. Most times, intensive chemotherapy regimens are associated with prolonged and profound pancytopenia when the risk of invasive fungal infection increases. After Candida and Aspergillus species, Mucormycosis is the third frequent fungal infection in hematology patients and it is associated with a reduced overall survival. When suspected, immediate treatment is needed. We present the case of 24-year-old patient diagnosed with Philadelphia chromosome positive acute lymphoblastic leukemia who developed right rhino-sino-orbital fungal infection with a favorable response to systemic antifungal treatment and noninvasive surgery. Later, patient refused consolidation and allogeneic hematopoietic stem cell transplant from an unrelated HLA matched donor but accepted the first generation tyrosine kinase inhibitor (Imatinib) and maintained a complete hematological and molecular response. ABBREVIATIONS: ENT = ear nose throat; BMB = bone marrow biopsy; ALL = acute lymphoblastic leukemia; TKI = tyrosine kinase inhibitor; IFI = invasive fungal infection; BMB = bone marrow biopsy; HE = hematoxylin and eosin; IHC = immunohistochemistry; CD = cluster of differentiation; ob = objective; Tdt = terminal deoxynucleotidyl transferase.