Fifty‐six adult patients with newly diagnosed acquired severe aplastic anemia (SAA) received horse antilymphocyte globulin (ALG), cyclosporin A (CyA), methylprednisolone (Mpred), granulocyte colony‐stimulating factor (G‐CSF) as first‐line therapy. The median age was 34 (range, 17–72) and median neutrophil count 0.280 × 10⁹/L. Trilineage hematologic recovery (at a median interval of 105 days from treatment) was seen in 46 patients (37 complete, 9 partial) after one (n = 38) or two (n = 8) courses of ALG. Cytogenetic abnormalities were observed in three unresponders, clonal hematologic disease in three complete responders, and relapse of marrow aplasia in four complete responders. Median follow up for surviving patients was 1,668 days (range, 237–4,012). The actuarial survival at 5 years was 82%, falling to 77.1% at 7 years and was stationary at 7 and 8 years. Survival was not influenced by the neutrophil count (72% vs. 87%, for neutrophils less than vs. greater than 0.2 × 10⁹/L; P = 0.54). Immunosuppressive treatment of SAA with the 4‐drug combination appears to be effective. The significant prognostic effect of an enduring increase of the white blood cell (WBC) count during G‐CSF treatment may suggest complete and partial response to therapy. In nonresponders, the WBC count either did not change or elevated values gradually returned to nearly their initial levels while the patients were still under G‐CSF treatment. In patients not responsive to treatment but living under CyA and G‐CSF, the possibility of developing cytogenetic abnormalities does not seem to be low, despite the absence of findings attributable to manifest myelodysplastic syndrome. Am. J. Hematol., 2007.

The prognosis is poor for relapsed or refractory (R/R) classical Hodgkin Lymphoma (cHL) patients. The brentuximab vedotin (Bv) and bendamustine (B) combination has been used as a preferable salvage regimen in R/R cHL patient trials. We retrospectively evaluated response rates, toxicities, and the survival in R/R cHL patients treated with the BvB combination. In a multi-centre real-life study, 61 R/R HL patients received intravenous doses of 1.8 mg/kg Bv on the first day plus 90 mg/m² B on the first and second days of a 21-day cycle as a second-line or beyond-salvage regimen. Patients’ median age at BvB initiation was 33 (range: 18–76 years). BvB was given as median third-line treatment for a median of four cycles (range: 2–11). The overall and complete response rates were 82% and 68.9%, respectively. After BvB initiation, the median follow-up was 14 months, and one- and two-year overall survival rates were 85% and 72%, respectively. Grade 3/4 toxicities included neutropenia (24.6%), lymphopenia (40%), thrombocytopenia (13%), anaemia (13%), infusion reactions (8.2%), neuropathy (6.5%), and others. The BvB combination could be given as salvage regimen aiming a bridge to autologous stem cell transplant (ASCT), in patients relapse after ASCT or to transplant-ineligible patients with manageable toxicity profiles.

Background/aim: JAK2V617F mutation is expressed in almost all polycthemia vera (PV), 55% of essential thrombocythemia (ET), and 65% of primary myelofibrosis (PMF) patients. Studies investigating phenotypic effects of JAK2V617F mutation on Philadelphia -negative myeloproliferative neoplasms (Ph-negative MPNs) have reported controversial results. This study aims to determine the impact of JAK2V617F mutation on clinical phenotype and outcome in Ph-negative MPNs. Materials and methods: Clinical correlates and long-term prognostic relevance of the JAK2V617F mutation were analyzed in 410 Ph-negative MPNs-170 ET, 135 PV, 105 PMF-from two institutions and followed for a mean of 76.7 months (SD 62.1) (mean 87 months (SD 67.8), 70.4 months (SD 56.4), 68 months (SD 57.4), respectively for ET, PV, and PMF). Two hundred and twenty-eight patients were genotyped for JAK2V617F mutation using the JAK2 Ipsogen MutaScreen assay, which involves allele-specific polymerase chain reaction (PCR), and 182 patients were genotyped using melting curve analysis. Results: In PV patients, JAK2V617F mutation was associated with higher rate in females, lower hemoglobin (Hgb) level, higher leukocyte and platelet count and higher prevalence of thrombosis (p = 0.008, p = 0.018, p = 0.001, p = 0.001, and p = 0.035, respectively). In ET patients, JAK2V617F mutation was associated with higher Hgb and hematocrit (Hct) levels and lower platelet count (p = 0.001, p = 0.001, and p = 0.001, respectively). JAK2V617F-negative ET patients showed a trend towards higher rate of leukemic transformation (p = 0.061). JAK2V617F mutation-positive PMF patients had higher leukocyte count, greater spleen size and showed a trend towards higher Hgb level (p = 0.019, p = 0.042, and p = 0.056, respectively). Among PMF patients with JAK2V617F mutation, the rate of female patients was lower (p = 0.001). Overall survival (OS) in Dynamic International Prognostic Scoring System (DIPSS) -plus high risk PMF patients was shorter compared to the other risk groups (p = 0.001). Leukemia-free survival (LFS) was shorter in DIPSS -plus high risk PMF patients than the other risk groups (p = 0.005). In the entire cohort of Ph-negative MPN patients, JAK2V617F mutation was associated with higher leukocyte count, higher Hgb and Hct levels and lower platelet count, higher frequency of phlebotomies, a trend towards older age, a trend towards greater spleen size, a trend towards a higher prevalence of risk factors for cardiovascular diseases and thrombosis (p = 0.001, p = 0.005, p = 0.001, p = 0.003, p = 0.004, p =0.052, p = 0.056, p = 0.052, and p = 0.059, respectively). Conclusion: In our study population, it was demonstrated that the presence of JAK2V617F mutation in ET patients was associated with PV-like phenotype. Our study also showed that the presence of the JAK2V617F mutation was associated with increased risk of thrombotic complications. Our results suggest that JAK2V617F mutation is associated with a more pronounced myeloproliferative phenotype in PMF patients. In a large number of Ph-negative MPN patients, our findings support that JAK2V617F mutation is associated with a more aggressive phenotype.

The impact of JAK2V617F allele burden on clinical course in Philadelphia-negative (Ph-negative) myeloproliferative neoplasms (MPNs) is not clear. We analyzed the clinical impact of JAK2V617F allele burden in a relatively large patient series of Ph-negative MPNs with long term follow-up. 228 patients with Ph-negative MPNs-118 essential thrombocythemia (ET), 84 primary myelofibrosis (PMF) and 26 polycythemia vera (PV)- were analyzed. JAK2 MutaScreen assay was used to quantify JAK2V617F allele burden in genomic DNA. In PV, high JAK2V617F allele burden was associated with a trend towards inferior OS. In ET, high JAK2V617F allele burden was associated with lower Hgb and hematocrit (Hct) levels, higher lactate dehydrogenase (LDH) levels, greater spleen size, increased bleeding and death rate. In PMF, high JAK2V617F allele burden was associated with higher leukocyte counts and greater spleen size. In the entire cohort, high allele burden was associated with higher leukocyte and lower platelet counts, higher LDH levels, greater spleen size, higher percentage of bleeding events, higher death rate and inferior OS. Our results remark high JAK2V617F allele burden is associated with more severe disease in PV and ET. In PMF, high JAK2V617F allele burden was associated with more pronounced myeloproliferative phenotype. In Ph-negative MPN, high allele burden was associated with more aggressive phenotype. Our data with long follow-up period support JAK2V617F allele burden may be a marker for predicting clinical phenotype in Ph-negative MPNs.