Low serum albumin level deteriorates prognosis in azacitidine-treated myelodysplastic syndromes patients - results of the PALG study 'PolAZA'.

BACKGROUND: Azacitidine (AZA) is the standard of care for higher-risk myelodysplastic syndrome (HR-MDS) patients ineligible for intensive therapy. Clinical outcome discrepancies reported in clinical trials and real-life settings stimulate the search for new prognostic factors. METHODS: We retrospectively evaluated 315 MDS, 20-30% blast acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML) patients treated with azacitidine in 12 centers cooperating within the Polish Adult Leukemia Group (PALG). RESULTS: The median number of AZA cycles was 7 (1-69) and 24% patients received fewer than 4 cycles (early failure, EF). Serum albumin level was an independent predictor of EF occurrence. Complete remission (CR) was obtained in 20% and partial remission (PR) in 12% of patients. Hematologic improvement - erythroid (HI-E), neutrophil (HI-N), or platelet (HI-P) was achieved in 51%, 36%, and 48% of patients, respectively. No factors significantly predicted CR or PR in the multivariate analysis. For HI-E and HI-P, lower LDH level predicted response. Median survival was 15 (13-19) months. Lower serum albumin level, serious infection and receiving <4 AZA cycles independently predicted a worse overall survival (OS) (p < 0.05). CONCLUSION: Serum albumin assessment before azacitidine treatment can help to identify patients with higher risk of early failure and worse clinical outcome.

Azacitidine for relapse of acute myeloid leukemia or myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation, multicenter PALG analysis.

OBJECTIVES: Relapse of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) belongs to the major causes of treatment failure. METHODS: Retrospective multicenter analysis of patients diagnosed with AML or MDS who had hematological relapse after allo-HSCT and were treated with azacitidine for this indication. RESULTS: Twenty-three patients receiving azacitidine as the first treatment of relapse (Group_1) and 8 patients receiving azacitidine after other treatment of relapse (Group_2) were included. There were 68% males, median age at initiation of azacitidine was 53 years (15-66). Median time to relapse was 3.5 months and 6.3 months in Group_1 and Group_2, respectively; median time from relapse to azacitidine 0.2 and 2.3 months. Azacitidine 75 mg/m2 , days 1-7, was administered in 78% and 75% of patients in Group_1 and Group_2, concomitant DLI in 48% and 50%. With median follow-up of 4.7 and 13.6 months, the median overall survival was 5.9 and 9.5 months. 17% and 37.5% patients proceeded to salvage allo-HSCT, with median OS of 11.6 months and not reached respectively. CONCLUSIONS: Azacitidine treatment for hematological relapse is associated with poor outcome; nevertheless, a proportion of patients may benefit from it, including patients receiving subsequent salvage allo-HSCT.

High efficacy of BGD (bendamustine, gemcitabine, and dexamethasone) in relapsed/refractory Hodgkin Lymphoma.

The optimal salvage therapy in relapsed/refractory Hodgkin lymphoma (R/R HL) has not been defined so far. The goal of this multicenter retrospective study was to evaluate efficacy and safety of BGD (bendamustine, gemcitabine, dexamethasone) as a second or subsequent line of therapy in classical R/R HL. We have evaluated 92 consecutive R/R HL patients treated with BGD. Median age was 34.5 (19-82) years. Fifty-eight patients (63%) had received 2 or more lines of chemotherapy, 32 patients (34.8%) radiotherapy, and 21 patients (22.8%) an autologous hematopoietic stem cell transplantation (autoHCT). Forty-four patients (47.8%) were resistant to first line of chemotherapy. BGD therapy consisted of bendamustine 90 mg/m2 on days 1 and 2, gemcitabine 800 mg/m2 on days 1 and 4, dexamethasone 40 mg on days 1-4. Median number of BGD cycles was 4 (2-7). The following adverse events ≥ 3 grade were noted: neutropenia (22.8%), thrombocytopenia (20.7%), anemia (15.2%), infections (10.9%), AST/ALT increase (2.2%), and skin rush (1.1%). After BGD therapy, 51 (55.4%) patients achieved complete remission, 23 (25%)-partial response, 7 (7.6%)-stable disease, and 11 (12%) patients experienced progression disease. AutoHCT was conducted in 42 (45.7%) patients after BGD therapy, and allogeneic HCT (alloHCT) in 16 (17.4%) patients. Median progression-free survival was 21 months. BGD is a highly effective, well-tolerated salvage regimen for patients with R/R HL, providing an excellent bridge to auto- or alloHCT.

Atypical chronic myeloid leukaemia: A case of an orphan disease-A multicenter report by the Polish Adult Leukemia Group.

Atypical chronic myeloid leukaemia (aCML) belongs to myelodysplastic/myeloproliferative neoplasms. Because of its rarity and changing diagnostic criteria throughout subsequent classifications, data on aCML are very scarce. Therefore, we at the Polish Adult Leukemia Group performed a nationwide survey on aCML. Eleven biggest Polish centres participated in the study. Altogether, 45 patients were reported, among whom only 18 patients (40%) fulfilled diagnostic criteria. Among misdiagnosed patients, myelodysplastic/myeloproliferative syndrome unclassifiable and chronic myelomonocytic leukaemia were the most frequent diagnoses. Thirteen patients were male, median age 64.6 years (range 40.4-80.9). The median parameters at diagnosis were as follows: white blood cell count 97 × 109 /L (23.8-342) with immature progenitors amounting at 27.5% (12-72), haemoglobin 8.6 g/dL (3.9-14.9), and platelet count 66 × 109 /L (34-833). Cytoreductive treatment was used in all patients, and 2 patients underwent allogeneic hematopoietic stem cell transplantation. The median overall survival was 14.1 months (95% CI, 7.2), with median acute myeloid leukaemia-free survival of 13.3 months (95% CI, 3.6-22.6). Cumulative incidence of acute myeloid leukaemia transformation after 1 year in aCML group was 12.5% (95% CI, 0%-29.6%). To conclude, aCML harbours a poor prognosis. Treatment options are limited, with allogeneic hematopoietic stem cell transplantation being the only curative method at present, although only a minority of patients are transplant eligible. Educational measures are needed to improve the quality of diagnoses.

Are myelodysplastic syndromes underdiagnosed in Poland? A report by the Polish Adult Leukaemia Group.

OBJECTIVES: The epidemiology of myelodysplastic syndromes (MDS) differs among countries. Here, we present the first epidemiological indices determined for Poland. METHODS: Twenty-one haematological centres participated in the study. Patients diagnosed with MDS and acute myeloid leukaemia (AML) with 20-29% blasts were enrolled. Data collection was conducted for strictly predefined period. RESULTS: The overall crude incidence rate for all MDS subtypes was 1.95 (95% CI, 1.81-2.09) per 100 000 person-years: 2.46 (95% CI, 2.24-2.69) for males and 1.47 (95% CI, 1.31-1.65) for females; after excluding AML cases, the indices were as follows: 2.35 (95% CI, 2.08-2.66) for males and 1.27 (95% CI, 1.08-1.5) for females. Prevalence rate was 6.2 per 100 000 persons (95% CI, 5.96-6.45), that is 6.86 (95% CI, 6.49-7.24) for males and 5.58 (95% CI, 5.26-5.92) for females. Both incidence and prevalence increased with increasing age. The most frequently diagnosed MDS subtype was refractory cytopenia with multilineage dysplasia (RCMD), responsible for 30.3% of all newly diagnosed MDSs. CONCLUSIONS: RCMD is the most frequent MDS subtype in Poland. Incidence and prevalence indices are lower than those reported for other populations, which probably results from inadequate diagnosis of potential cases of this disease.