Background: After discontinuing ruxolitinib, the outcome of patients with myelofibrosis reportedly has been poor. The authors investigated whether disease characteristics before the receipt of ruxolitinib may predict drug discontinuation in patients with myelofibrosis and whether reasons for drug discontinuation, disease phase at discontinuation, and salvage therapies may influence the outcome.Methods: A centralized electronic clinical database was created in 20 European hematology centers, including clinical and laboratory data for 524 patients who received ruxolitinib for myelofibrosis.Results: At 3 years, 40.8% of patients had stopped ruxolitinib. Baseline predictors of drug discontinuation were: intermediate‐2–risk/high‐risk category (Dynamic International Prognostic Score System), a platelet count <100 ×10⁹ per liter, transfusion dependency, and unfavorable karyotype. At last contact, 268 patients (51.1%) had discontinued therapy, and the median drug exposure was 17.5 months. Fifty patients (18.7%) died while taking ruxolitinib. The reasons for discontinuation in the remaining 218 patients were the lack (22.9%) or loss (11.9%) of a spleen response, ruxolitinib‐related adverse events (27.5%), progression to blast phase (23.4%), ruxolitinib‐unrelated adverse events (9.2%), and allogeneic transplantation during response (5.1%). The median survival after ruxolitinib was 13.2 months and was significantly better in the 167 patients who discontinued ruxolitinib in chronic phase (27.5 vs 3.9 months for those who discontinued in blast phase; P < .001). No survival differences were observed among patients who discontinued ruxolitinib in chronic phase because of lack of response, loss of response, or ruxolitinib‐related adverse events. The use of investigational agents and/or ruxolitinib rechallenge were associated with improved outcome.Conclusions: The survival of patients with myelofibrosis after discontinuation of ruxolitinib is poor, particularly for those who discontinue in blast phase. Salvage therapies can improve outcome, emphasizing the need for novel therapies.

The use of all-trans retinoic acid (ATRA) in combination with chemotherapy has markedly improved the prognosis for patients with acute promyelocytic leukemia (APL); the higher complete remission (CR) and survival rates now reported in this disease almost approach those obtained for other highly curable hematologic malignancies. Of 77 patients with APL who were consecutively treated at a single institution and who achieved CR after induction and consolidation therapy, 5 (6.5%) acquired therapy-related myelodysplasia (tMDS), acute myelogenous leukemia (AML), or both (tMDS–AML). Of these, 3 of 46 (6.5%) patients received front-line chemotherapy with or without ATRA and acquired tMDS–AML while in first remission of APL. Two underwent repeated chemotherapy cycles with ATRA because of APL relapse and acquired tMDS–AML while in the second or third remission of APL. In 2 patients, clinical and biologic characteristics of tMDS–AML were as expected for postalkylating forms (long latency, MDS phase preceding AML, karyotypic aberrations involving chromosomes 5 or 7), even though one of them had not previously received alkylating drugs. Three of the 5 patients died shortly after tMDS–AML diagnosis, one is alive with tMDS, and one is alive and in CR after allogeneic bone marrow transplantation. The occurrence of tMDS–AML after successful therapy for APL is an emerging problem. The availability of prognostic score systems at initial diagnosis and monitoring of residual disease by polymerase chain reaction might allow better tailoring of treatment intensity in APL to spare unnecessary toxicity and to minimize the risk for tMDS–AML in patients who are presumably cured.

Summary.Between January 1985 and December 1992, 104 consecutive patients with symptomatic myelofibrosis with myeloid metaplasia (MMM) [splenic enlargement > 5 cm and/or transfusional requirement or Hb < 10 g/dl and/or white blood cell (WBC) count > 20 × 10⁹/l and/or platelets > 1·0 × 10⁹/l] received low‐dose Melphalan (2·5 mg/3 times/week) to evaluate the efficacy and toxicity of this approach. Among 99 evaluable patients, 66 (66·7%) achieved a response after a median time of 6·7 months: 26 (26·3%) had a normalization of all clinical and haematological parameters (complete response, CR) and 40 (40·4%) showed an improvement > 50% (partial response, PR). Thirty‐three patients (33·3%) were resistant. Reversible haematological toxicity was the most common complication. Median durations of CR and PR were 28·4 and 26 months respectively: median survival of CR + PR patients was 71·2 months (95%CI: 33·8–108·7) versus 36·5 months (95%CI: 24·5–48·5) for the non‐responders (log‐rank test,P= 0·002). In the multivariate analysis, the following variables were significantly associated with a shorter survival: anaemia [hazard risk (HR) = 2·7], WBC count > 20 × 10⁹/l (HR = 2·4) and not achieving any type of response, either partial or complete (HR = 3·9). In conclusion, Melphalan could be a promising first‐line option for MMM patients with clinical or haematological symptoms requiring treatment.

Summary: This randomized phase III clinical trial explored the efficacy of DaunoXome (DNX) versus Daunorubicin (DNR) in acute myeloid leukaemia (AML) patients aged >60 years. Three hundred and one AML patients were randomized to receive DNR (45 mg/m² days 1–3) or DNX (80 mg/m² days 1–3) plus cytarabine (AraC; 100 mg/m² days 1–7). Patients in complete remission (CR) received a course of the same drugs as consolidation and then were randomized for maintenance with AraC+ all trans retinoic acid or no further treatment. Among 153 patients in the DNR arm, 78 (51·0%) achieved CR, 55 (35·9%) were resistant and 20 (13·1%) died during induction. Among 148 patients in the DNX arm, 73 (49·3%) achieved CR, 47 (31·8%) were resistant and 28 (18·9%) died during induction. Univariate analysis showed no difference as to induction results. After CR, DNX showed a higher incidence of early deaths (12·5% vs. 2·6% at 6 months, P = 0·053) but a lower incidence of relapse beyond 6 months (59% vs. 78% at 24 months, P = 0·064), with a cross in overall survival (OS) and disease‐free survival (DFS) curves and a later advantage for DNX arm after 12 months from diagnosis. DNX seems to improve OS and DFS in the long‐term follow‐up, because of a reduction in late relapses.