The optimal treatment of primary mediastinal large B-cell lymphoma (PMLBCL) is still undefined. In the absence of randomised studies, we retrospectively analysed:

Summary. About 30% of patients with severe aplastic anaemia (SAA) unresponsive to one course of immunosuppressive (IS) therapy with antithymocyte or antilymphocyte globulin can achieve complete or partial remission after a second IS treatment. Among various second-line treatments, rabbit ATG (r-ATG) could represent a safe and effective alternative to horse ALG (h-ALG). In a multicentre study, 30 patients with SAA (17 males and 13 females, median age 21 years, range 2±67) not responding to a ®rst course with h-ALG plus cyclosporin (CyA) and granulocyte colony stimulating factor (G-CSF), were given a second course using r-ATG (3´5 mg/kg/d for 5 d), CyA (5 mg/kg orally from day 1 to 180) and G-CSF (5 mg/kg subcutaneously from day 1 to 90). The median interval between ®rst and second treatment was 151 d (range 58±361 d). No relevant side-effects were observed, but one patient died early during treatment because of sepsis. Overall response, de®ned as transfusion independence, was achieved in 23/30 (77%) patients after a median time of 95 d (range 14±377). Nine patients (30%) achieved complete remission (neutrophils >2´0´10 9 /l, haemoglobin >11 g/dl and platelets >100´10 9 /l). The overall survival rate was 93% with a median follow-up of 914 d (range 121±2278). So far, no patient has relapsed. Female gender was signi®cantly associated with a poorer likelihood to respond (P 0´0006). These data suggest that r-ATG is a safe and effective alternative to h-ALG for SAA patients unresponsive to ®rst-line IS treatment.

All-trans-retinoic acid (ATRA) has greatly modified the prognosis of acute promyelocytic leukemia; however, the role of maintenance in patients in molecular complete remission after consolidation treatment is still debated.

Only limited data are available regarding myocardial iron overload in adult patients with transfusion dependent acquired anemias. To address this topic using MRI T2* we studied 27 consecutive chronic transfusion dependent patients with acquired anemias: (22 myelodysplastic syndrome, 5 primary myelofibrosis). Cardiac MRI T2* values obtained ranged from 5.6 to 58.7 (median value 39.8) milliseconds. Of the 24 analyzable patients, cardiac T2* correlated with transfusion burden (p=0.0002). No patient who had received less than 290 mL/kg of packed red blood cells (101 units=20 grams of iron) had a pathological cardiac T2* value (< 20 ms). All patients who had received at least 24 PRBC units showed MRI T2* detectable hepatic iron (liver T2* value ≤6.3 ms). Only patients with severe hepatic iron overload (T2* <1.4 ms) showed cardiac T2* value indicative of dangerous myocardial iron deposition. Serum ferritin was not significantly correlated with cardiac T2* (p=0.24). Gradient echo T2* magnetic resonance imaging provides a rapid and reproducible method for detecting myocardial iron overload which developed after a heavy transfusion burden equal to or greater than 290 mL/kg of packed red blood cell units.

High-dose (200 mg/m 2 , MEL200) and intermediate-dose melphalan (100 mg/ m 2 , MEL100) showed significant activity in myeloma. In a phase 3 study, 298 patients were randomly assigned to receive 2 autologous transplantations after conditioning with MEL200 or MEL100. Ninetysix of 149 (64%) completed MEL200 and 103 of 149 (69%) MEL100. Best response to MEL200 was: complete remission 22 of 149 (15%); partial remission 95 of 149 (64%), for an overall response rate of 79%. Best response to MEL100 was: complete remission 12 of 149 (8%); partial remission 95 of 149 (64%), for an overall response rate of 72%. Overall survival did not differ (P ‫؍‬ .13); median progression-free survival (31.4 vs 26.2 months, P ‫؍‬ .01), median time to progression (34.4 vs 27.0 months, P ‫؍‬ .014) were longer in the MEL200. Treatment-related mortality was 3.1% in the MEL200 and 2.9% in the MEL100 group. Severe neutropenia and infections were marginally superior, whereas severe thrombocytopenia, mucositis, gastrointestinal adverse events, and the overall occurrence of at least 1 nonhematologic grade 3 or 4 adverse event were significantly higher in the MEL200 cohort. We conclude that MEL200 leads to longer remission duration and should be considered the standard conditioning regimen for autologous transplantation. This study was registered at www.clinicaltrials.gov as #NCT00950768. IntroductionSeveral studies support the benefit of high-dose melphalan with stem cell rescue in patients with newly diagnosed multiple myeloma. [1][2][3] Results from randomized trials are in favor of tandem autologous transplantation rather than only 1 procedure, even though a real benefit remains to be determined. 4,5 Most conditioning regimens have been based on either melphalan alone or in combination with other agents. Melphalan at 200 mg/m 2 (MEL200) is considered the standard dose for conditioning patients younger than 65 years. 6 Older age and comorbidities may become limiting factors. In a retrospective case-matched study, 90 newly diagnosed patients treated with 2 courses of melphalan at 100 mg/m 2 (MEL100) were compared with a control group of 90 pair mates, matched for serum ␤-microglobulin levels and Durie-Salmon clinical stage, and treated up-front with 2 MEL200 courses. 7 Median progression-free survival (PFS) was significantly superior in the MEL200 group, but overall survival (OS) was not different. Moreover, hematologic and nonhematologic toxicities were significantly reduced in the MEL100 group. Here, we report a phase 3 clinical trial comparing 2 doses of melphalan, MEL200 versus MEL100, in newly diagnosed multiple myeloma. The underlying hypothesis was that rather than give 2 very intensive preparative regimens before autologous stem cell infusions, providing effective myeloma cell kill, a less toxic reducedintensity conditioning would be better tolerated, especially in older patients, and equally effective. Methods PatientsFrom October 2001 to July 2006, 298 newly diagnosed myeloma patients younger than 65 years were enrolled in a prospecti...