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1.
Int J Hematol ; 116(6): 922-928, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35972605

ABSTRACT

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ruxolitinib (RUX), an oral JAK1 and JAK2 inhibitor, has recently been approved for patients with SR-aGVHD. The aim of this study was to evaluate RUX efficacy and toxicity in a real-world setting. Eighteen patients received RUX at 5 mg or 10 mg twice a day after a median 3 lines of prior unsuccessful immunosuppressive therapy. Median time on RUX therapy was 28 days (range 7-129). Five patients (28%) responded to RUX, including 4 complete responses and 1 partial response. Response to RUX was irrespective of aGVHD grade and the number of involved organs. One-year overall survival (OS) was 60% for RUX-responders versus 31% for non-responders (p = ns). Treatment duration greater than 29.5 days was found to have a positive impact on OS (p < 0.007). Major adverse events during RUX treatment were grade 3-4 thrombocytopenia (61% of patients) and cytomegalovirus reactivation (50%). After median follow-up of 55 days (range 29-706), 14 patients (78%) died, mainly due to further progression of GVHD. RUX may represent a valuable therapeutic option for some patients with advanced SR-aGVHD, but more studies are warranted.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Graft vs Host Disease/drug therapy , Graft vs Host Disease/etiology , Pyrimidines/therapeutic use , Pyrazoles/adverse effects , Nitriles/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Steroids/therapeutic use , Acute Disease , Retrospective Studies
2.
Ann Hematol ; 99(8): 1845-1853, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32333156

ABSTRACT

Acute myeloid leukemia (AML) with fetal liver tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is associated with poor prognosis, and allogeneic stem cell transplantation (Allo-SCT) seems to be the preferred therapeutic approach. However, the predictors of post-transplant outcomes were not well-defined. The aim of the study was to evaluate the significance of FLT3/ITD mutation by polymerase chain reaction as minimal residual disease (MRD) marker of outcomes after transplantation. We identified 43 patients (28 females and 15 males) with FLT3-mutated AML at the median age of 45 years who were allografted between 2009 and 2019. Hematological status at transplant was as follows: the first complete remission (CR1) in 29 patients, CR2 in 5, and 9 patients were transplanted in marrow aplasia (MA). Twenty-seven patients were FLT3 MRD negative at transplant. Median time from diagnosis to transplant was 16.7 months. Post-allograft CR rate was 88%. The relapse incidence (RI) was lower for patients who were FLT3 MRD negative at transplant when compared with those with FLT3 MRD positivity (41% vs 59%; p = 0.01). The patients who eradicated FLT3/ITD at day + 30 after transplant had lower RI than those with detectable FLT3/ITD (23% vs 76%; p = <0.001). The 2-year LFS and OS were 53% and 54%, with the median OS and LFS of 28 months and 27 months, respectively. Patients with CR1/2 and FLT3 MRD(-) had a 2-year OS of 80%. The FLT3 MRD negativity at transplant prolonged LFS in multivariate analysis (HR 5.3 95%CI 1.97-14.2); p < 0.001), whereas FLT3 MRD negativity and unrelated donor predicted favorable OS.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Leukemia, Myeloid, Acute/therapy , Mutation , Stem Cell Transplantation , Unrelated Donors , fms-Like Tyrosine Kinase 3/genetics , Adult , Aged , Allografts , Disease-Free Survival , Female , Follow-Up Studies , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Predictive Value of Tests , Survival Rate
3.
Pathol Oncol Res ; 25(3): 1175-1180, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30613922

ABSTRACT

The administration of azacitidine (AZA) was found to be more effective than conventional care regimen (CCR) in patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) with lower blast count. We designed a study to determine efficacy and safety of AZA therapy in "real life" patients with MDS, CMML and AML. The study included 83 patients (65% male) with a median age at diagnosis of 68 years. 43 patients were diagnosed with higher-risk MDS, 30 had AML and 10-CMML. Median AZA dose was comparable between treated groups. AZA dose reduction was required for 44% of MDS, 17% of AML and 25% of CMML patients. Complete remission (CR) was achieved in 14% of MDS, 7% of AML and 10% of CMML patients. Overall response rate was following: 27% for MDS, 20% for AML and 20% for CMML. Estimated OS at 12 months was 75% for MDS, 60% for AML and 75% for CMML. Median follow-up for MDS/AML/CMML from AZA initiation to last follow-up was 9.0, 9.4 and 9.4 months, respectively. The most common toxicity of AZA therapy was myelosuppression and infections. AZA treatment was effective in a limited number of patients with acceptable safety profile.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myelomonocytic, Chronic/drug therapy , Myelodysplastic Syndromes/drug therapy , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Leukemia, Myeloid, Acute/pathology , Leukemia, Myelomonocytic, Chronic/pathology , Male , Middle Aged , Myelodysplastic Syndromes/pathology , Retrospective Studies , Safety , Survival Rate , Treatment Outcome
4.
Indian J Hematol Blood Transfus ; 32(Suppl 1): 62-5, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27408357

ABSTRACT

Leukemic transformation in patients diagnosed with polycythemia vera (PV) is associated with poor prognosis and median survival not exceeding 3 months. To date only a few cases of post-PV acute lymphoblastic leukemia (ALL) have been reported. A 64-year-old female patient developed ALL 4 years after she had met PV criteria. At PV diagnosis a molecular study was positive for the JAK2V617F mutation. Due to high risk features (history of deep vein thrombosis) she was treated with hydroxyurea (HU) with moderate efficacy. She became anemic and thrombocytopenic with mild leukocytosis while still on HU. Blood and bone marrow smears revealed 40 and 100 % of blast cells, respectively. The immunophenotyping of blasts was consistent with a diagnosis of early precursor B cell ALL. She was found to be positive for the JAK2V617F mutation. Patient received an ALL induction regimen and achieved complete remission with negative minimal residual disease by flow cytometry. The post-chemotherapy study for the JAK2V617F mutation was positive. Patient has remained in remission for 4 months. A suitable donor searching was initiated. Post-PV ALL is an extremely rare phenomenon. Due to poor prognosis, an allogeneic stem cell transplantation should be considered in fit patients who achieved remission.

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