Secondary acute myeloid leukemia (sAML) poorly responds to conventional treatments and allogeneic stem cell transplantation (HSCT). We evaluated toxicity and efficacy of CPX-351 in 71 elderly patients (median age 66 years) with sAML enrolled in the Italian Named (Compassionate) Use Program. Sixty days treatment-related mortality was 7% (5/71). The response rate at the end of treatment was: CR/CRi in 50/71 patients (70.4%), PR in 6/71 (8.5%), and NR in 10/71 (19.7%). After a median follow-up of 11 months relapse was observed in 10/50 patients (20%) and 12 months cumulative incidence of relapse (CIR) was 23.6%. Median duration of response was not reached. In competing risk analysis, CIR was reduced when HSCT was performed in first CR (12 months CIR of 5% and 37.4%, respectively, for patients receiving (=20) or not (=30) HSCT, p = 0.012). Twelve-months OS was 68.6% (median not reached). In landmark analysis, HSCT in CR1 was the only significant predictor of longer survival (12 months OS of 100 and 70.5%, for patients undergoing or not HSCT in CR1, respectively, p = 0.011). In conclusion, we extend to a real-life setting, the notion that CPX is an effective regimen for high risk AML patients and may improve the results of HSCT.

The outcome of relapsed or refractory (R/R) T‐cell acute lymphoblastic leukemia/lymphoma (T‐ALL/T‐LBL) in adults is poor, with less than 20% of patients surviving at 5 years. Nelarabine is the only drug specifically approved for R/R T‐ALL/T‐LBL, but the information to support its use is based on limited available data. The aim of this observational phase four study was to provide recent additional data on the efficacy and safety of nelarabine in adults with R/R T‐ALL/T‐LBL and to evaluate the feasibility and outcome of allogeneic hematopoietic stem cell transplant (SCT) after salvage with nelarabine therapy. The primary endpoints were overall response rate (ORR) and overall survival (OS). Additional endpoints were safety, SCT rate and post‐SCT OS. Between May 2007 and November 2018, 118 patients received nelarabine salvage therapy at 27 Italian hematology sites. The median age was 37 years (range 18‐74 years), 73% were male, 77 had a diagnosis of T‐ALL and 41 of T‐LBL, and 65/118 (55%) had received more than two lines of therapy. The median number of nelarabine cycles was two (range 1‐4); 43/118 (36%) patients had complete remission (CR), 16 had partial remission (14%) and 59 (50%) were refractory, with an ORR of 50%. The probability of OS, from the first dose of nelarabine, was 37% at 1 year with a median survival of 8 months. The OS at 1 year was significantly better for the 47 patients (40%) who underwent SCT after nelarabine salvage therapy (58% vs 22%, log‐rank P < .001). The probability of OS at 2 and 5 years from SCT was 46% and 38%, respectively. Seventy‐five patients (64%) experienced one or more drug‐related adverse events (AE). Grade III‐IV neurologic toxicities were observed in 9/118 (8%) of cases and thrombocytopenia or/and neutropenia (grade III‐IV) were reported in 41% and 43% of cases, respectively. In conclusion, this is one of the largest cohorts of adult patients with R/R T‐ALL/T‐LBL treated in real life with nelarabine. Taking into account the poor prognosis of this patient population, nelarabine represents an effective option with an ORR of 50% and a CR rate of 36%. In addition, 40% of cases following nelarabine salvage therapy could undergo SCT with an expected OS at 2 and 5 years of 46% and 38%, respectively. The safety profile of nelarabine was acceptable with only 8% of cases showing grade III‐IV neurological AE.

Serum levels of tumor necrosis factor-α (TNF-α) and of erythropoietin (Epo) have been evaluated in 100 patients with B-cell chronic lymphocytic leukemia (CLL) in order to determine whether these factors could be significant in the development of anemia, which was observed in some cases with advanced disease. In our series of patients, TNF-α serum levels had an inverse correlation with hemoglobin levels (r = –0.813). In patients with anemia, the serum levels of TNF-α were significantly higher (p = 0.022) than in those without anemia (186.7 ± 84.7 vs. 39.8 ± 20.7 pg/ml). Serum Epo levels were also significantly (p = 0.0003) increased in CLL patients with anemia compared to those without (134.1 ± 225.9 vs. 12.3 ± 4.8 mU/ml). The ratio of observed/predicted (O/P) serum Epo was adequate (>0.8) for the degree of anemia in 70% of patients with anemia and inadequate in the remaining 30%. In the latter, the mean serum TNF-α level was significantly higher (p = 0.005) than the mean for the anemic cases with an adequate O/P ratio of serum Epo (234.1 vs. 166.4 pg/ml). These data suggest that although CLL anemia is not characterized by inadequate Epo production, in some CLL patients this factor may be correlated. In these cases, the levels of TNF-α were significantly higher than in other anemic cases. Compared to other CLL patients with anemia, these CLL patients might better respond to therapy with recombinant human Epo in pharmacological doses.

Summary Background Rhodotorula spp are uncommon yeasts able to cause infections with high mortality rates. Rhodotorula infections have been associated with the presence of central venous catheter (CVC), immunosuppression, exposure to antifungals and the presence of either solid or haematologic malignancies. However, in this latter setting, only a few cases have so far been reported. Objectives We have conducted a survey for Rhodotorula infections in haematologic patients. Methods Patients’ clinical and microbiological data were collected and correlated to the outcome. Results A total of 27 cases were detected from 13 tertiary care hospitals. About 78% and 89% of patients had acute leukaemia and CVC. About 70% of patients were exposed to prophylaxis with azoles, mainly posaconazole (37%), 59% were severely neutropenic and 37% underwent allogeneic stem cell transplantation (alloSCT). The most frequent treatments were liposomal amphotericin B (L‐AmB) and CVC removal in 17 and 16 patients, respectively. One month post‐diagnosis, mortality was 26% and was associated with the presence of mucositis (P = 0.034). Conclusions Our study shows that Rhodotorula spp should be considered as aetiologic agents of breakthrough infections in acute leukaemia patients with a CVC, mucositis, who receive prophylaxis with azoles, including posaconazole, and/or undergo alloSCT. Prompt measures, such as L‐AmB administration and CVC removal, should be carried out to avoid the high mortality risk of Rhodotorula infections.

We report the use of Alemtuzumab (Campath-1H) as salvage treatment in three patients with advanced mycosis fungoides/Sézary syndrome who had previously been treated with conventional chemotherapy. Two patients (case 1 and case 2), aged 42 and 68 yr, respectively, were heavily pretreated (more than three prior therapy regimens, including autologous transplant in case 2) and refractory to conventional chemotherapy, and the third patient (case 3), aged 80 yr, who had refused any chemotherapy, had been resistant to treatment with cyclosporine and steroids. Campath-1H was administered intravenously, after an escalating dose from 3 to 10 mg, at the dose of 30 mg, three times weekly, to a total dose of 1080, 223, and 480 mg, respectively. The patients with Sézary syndrome (case 2 and case 3) showed clearance of circulating Sézary cells and clinical improvement of the skin lesions after 2 wk of treatment. Two patients (case 1 and case 3) completed the treatment (12 and 6 wk) without significant toxicity, the former achieving a partial response and the latter a clinical complete response. The patient (case 2), who suffered from ischemic cardiopathy and diabetes, quickly achieved a clinical improvement of the Sézary syndrome, but he died because of a myocardial infarction after 3 wk of treatment. Our report shows that the treatment with Campath-1H is active even in patients with advanced refractory mycosis fungoides/Sézary syndrome. Further clinical observations on a larger cohort of patients are needed to establish if Campath-1H may have a role as first line therapy in addition to conventional therapy including chemotherapy.