A Case of Successful Allogeneic Hematopoietic Stem Cell Transplantation in a Severely Underweight Patient with Aplastic Anemia

Allogeneic hematopoietic stem cell transplantation (alloHSTC) is considered definitive and the most effective treatment for young patients diagnosed with severe aplastic anemia. Low body mass index (BMI) is known to be associated with poorer outcomes in stem cell transplantation and higher mortality risks. Malnutrition negatively affects the patient’s ability to mobilize stem cells, therefore reducing patients’ stem cell production, although the patient’s nutritional status improvement with enteral and parenteral nutrition may reduce the risks of stem cell graft failure and graft-vs-host disease (GVHD) occurrence. The present report demonstrates a severely underweight patient with aplastic anemia and a BMI of 11 kg/m2 who was unsuccessfully treated with immunosuppressive therapy followed by alloHSTC

Combination of Dabrafenib and Trametinib for the treatment of relapsed and refractory multiple myeloma harboring BRAF V600E mutation

Multiple myeloma (MM) is an incurable plasma cell neoplasia characterized by relapsed and/or refractory (R/R) disease course, which poses a major therapeutic challenge. New therapies, including BRAF V600E mutation targeting, may become a new treatment option for R/R MM. In combination with mitogen-activated protein kinase inhibitors (MEKi), BRAF inhibitors (BRAFi) could provide better tailored clinical management, although experience in this field is lacking. To this date, there is only one case describing R/R MM treatment with BRAFi vemurafenib and MEKi cobimetinib. This is the first case presenting a R/R MM patient treated with BRAFi dabrafenib and MEKi trametinib

Potential Prognostic Markers for Relapsed/Refractory vs. Responsive Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogeneous disease. A significant proportion of AML patients is refractory to clinical treatment or relapses. Our aim is to determine new potential AML clinical treatment prognosis markers. We investigated various cell fate and epigenetic regulation important gene level differences between refractory and responsive AML patient groups at diagnosis stage and after clinical treatment using RT-qPCR. We demonstrated that oncogenic MYC and WT1 and metabolic IDH1 gene expression was significantly higher and cell cycle inhibitor CDKN1A (p21) gene expression was significantly lower in refractory patients’ bone marrow cells compared to treatment responsive patients both at diagnosis and after clinical treatment. Moreover, we determined that, compared to clinical treatment responsive patients, refractory patients possess a significantly higher gene expression of histone deacetylase 2 (HDAC2) and epigenetic DNA modulator TET1 and a significantly lower gene expression of lysine acetyltransferase 6A (KAT6A) and nucleosome remodeling and deacetylase (NuRD) complex component GATAD2A. We suggest that MYC, WT1, IDH1, CDKN1A, HDAC2, TET1, KAT6A and GATAD2A gene expression changes might characterize refractory AML. Thus, they might be useful for AML prognosis. Additionally, we suggest that epigenetic modulation might be beneficial in combination with standard treatment

Outcomes and Risk Factors of Critically Ill Patients with Hematological Malignancy. Prospective Single-Centre Observational Study

Background and Objectives: Oncohematological patients have a high risk of mortality when they need treatment in an intensive care unit (ICU). The aim of our study is to analyze the outcomes of oncohemathological patients admitted to the ICU and their risk factors. Materials and Methods: A prospective single-center observational study was performed with 114 patients from July 2017 to December 2019. Inclusion criteria were transfer to an ICU, hematological malignancy, age >18 years, a central line or arterial line inserted or planned to be inserted, and a signed informed consent form. Univariate and multivariable logistic regression models were used to evaluate the potential risk factors for ICU mortality. Results: ICU mortality was 44.74%. Invasive mechanical ventilation in ICU was used for 55.26% of the patients, and vasoactive drugs were used for 77.19% of patients. Factors independently associated with it were qSOFA score ≥2, increase of SOFA score over the first 48 h, mechanical ventilation on the first day in ICU, need for colistin therapy, lower arterial pH on arrival to ICU. Cut-off value of the noradrenaline dose associated with ICU mortality was 0.21 μg/kg/min with a ROC of 0.9686 (95% CI 0.93–1.00, p < 0.0001). Conclusions: Mortality of oncohematological patients in the ICU is high and it is associated with progression of organ dysfunction over the first 48 h in ICU, invasive mechanical ventilation and need for relatively low dose of noradrenaline. Despite our findings, we do not recommend making decisions regarding treatment limitations for patients who have reached cut-off dose of noradrenaline

Gilteritinib maintenance after allogeneic stem cell transplantation for FLT3 mutated acute myeloid leukemia

A proportion of FLT3m AML patients remain in prolonged CRs on Gilteritinib maintenance after alloSCT despite prior exposure to Midostaurin, Gilteritinib and Venetoclax. Conversion from positive MRD to negative MRD was confirmed in several cases. Relapses post-Gilteritinib maintenance were enriched with RAS pathway mutations and clinically relevant clonal evolution such as loss of FLT3m or gain of BCR-ABL1. The toxicity of Gilteritinib was manageabl

Azacitidine in combination with 14-day venetoclax versus azacitidine monotherapy for myelodysplastic syndrome with increased blasts-2 in clinical practice setting

Background: Azacitidine (AZA) is the standard-of-care for myelodysplastic syndromes with increased blasts-2 (MDS-IB2), however, due to the limited efficacy there is an unmet need for more effective therapies. Recently, promising phase 1 data of Azacitidine and Venetoclax (AZA+VEN) have been published and the phase 3 Verona trial is ongoing. Herein, we compared our institutional experience of AZA+VEN doublet with AZA monotherapy for the treatment of MDS-IB2. Aims: The aim of our study was to compare the efficacy and toxicity of AZA+VEN with AZA monotherapy for MDS-IB2 treatment. Methods: We conducted an observational, retrospective study. The patients were older than 18 years of age, had newly diagnosed MDS-IB2, and were treated with either AZA+VEN or AZA monotherapy. All patients provided informed consent for treatment and data collection. The AZA+VEN regimen consisted of Venetoclax 400mg/d on days 1-14 with Azacitidine 75mg/m2 on days 1-7. AZA patients received Azacitidine 75mg/m2 on days 1-7. The treatment cycles were administered every 28 days or with longer intervals depending on the hematological recovery and adverse events. Eligible responders could proceed to allogeneic stem cell transplantation (alloSCT). We evaluated baseline characteristics, IPSS-R, IPPS-M values, marrow CR (mCR), CR, CRi rates, overall survival (OS), time to ANC>1x109 and PLT>100x109 recovery from the start of the treatment, CTCAE v5.0 grade 3-5 non-hematological toxicity, day-30, day-60 mortality rates. Results: 16 patients (10 female) were treated with AZA+VEN whereas 17 (7 female) patients received AZA. Median age and ECOG values were 59 years (38-71) and 1 (0-2) in the AZA+VEN cohort compared to 74 years (53-84) and 2 (1-3) in the AZA group, respectively (p<0.001, p=0.026). The median IPSS-R value was 7.5 (5-10) in the AZA+VEN group and 6 (5-8) in AZA patients (p=0.004). The median IPSS-M value was 2.57 (0.55-4.57) in the AZA+VEN group, whereas data was not available for AZA patients. Complex karyotype was identified in 5/16 (31%) and 3/17(18%) in AZA+VEN and AZA patients, respectively (p=0.438). A median of 1 (1-3) AZA+VEN treatment cycle was administered, whereas AZA was given for a median of 4 (1-27) cycles. The mCR rate was 12/15 (75%) in the AZA+VEN patients and 6/15 (40%) in the AZA group (p=0.06). The CR+CRi rate was 9/15 (60%) in the AZA+VEN group in comparison to 5/15 (33%) in the AZA patients (p=0.272). 5/16 (31%) of AZA+VEN patients were bridged to alloSCT, whereas none of the AZA was allotransplanted. The median follow-up was 10.3 months in the AZA+VEN cohort and 31.3 months in the AZA group. The median OS was 6.8 months (3.2-22.1) and 14.1 months (6.9-17.6) in the AZA+VEN and AZA groups, respectively (p=0.436). 2-year OS was 20% in both groups (Figure 1). The median time to ANC and PLT recovery was 50 (4-165) and 60 days (21-94) in the AZA+VEN cohort compared to 38 (35-74) and 48 days (28-129) in AZA patients, respectively (p=0.66, p=0.464). Grade 3-5 adverse events occurred in 7/16 (44%) of AZA+VEN patients in comparison to 7/17 (41%) in the AZA group (p=0.881). Day-30 and day-60 mortality rates were 2/16 (13%) and 3/16 (19%) in the AZA+VEN group. No early deaths occurred in the AZA cohort. Summary/Conclusion: AZA+VEN treatment demonstrated higher response rates in MDS-IB2 patients however, this did not translate into prolonged survival compared to AZA monotherapy. Trends toward longer hematological recovery and higher early mortality were evident in the AZA+VEN group. Nevertheless, our real-life results should be interpreted with caution due to the small patient numbers, significant intergroup differences, and the retrospective nature of the study

HDAC and HMT inhibitors in combination with conventional therapy: a novel treatment option for acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is characterized by PML-RARA translocation, which causes the blockage of promyelocyte differentiation. Conventional treatment with Retinoic acid and chemotherapeutics is quite satisfactory. However, there are still patients who relapse or develop resistance to conventional treatment. To propose new possibilities for acute leukemia treatment, we studied the potential of histone deacetylase (HDAC) inhibitor and histone methyl transferase (HMT) inhibitor to enhance conventional therapy in vitro and ex vivo. NB4 and HL60 cell lines were used as an in vitro model; APL patient bone marrow mononuclear cells were used as an ex vivo model. Cell samples were treated with Belinostat (HDAC inhibitor) and 3-Deazaneplanocin A (HMT inhibitor) in combination with conventional treatment (Retinoic acid and Idarubicin). We demonstrated that the combined treatment used in the study had slightly higher effect on cell proliferation inhibition than conventional treatment. Also, enhanced treatment showed stronger effect on induction of apoptosis and on suppression of metabolism. Moreover, the treatment accelerated granulocytic cell differentiation and caused chromatin remodelling (increased H3K14 and H4 acetylation levels). In vitro and ex vivo models showed similar response to the treatment with different combinations of 3-Deazaneplanocin A, Belinostat, Retinoic acid, and Idarubicin. In conclusion, we suggest that 3-Deazaneplanocin A and Belinostat enhanced conventional acute promyelocytic leukemia treatment and could be considered for further investigations for clinical use

Revumenib in patients with acute leukemias: compassionate use program experience

In this compassionate use program, which included heavily pretreated pts, disease responses were observed. Several pts who started REV as maintenance post-HSCT experienced prolonged remissions. No new safety signals were reported