Nivolumab combined with brentuximab vedotin with or without mediastinal radiotherapy for relapsed/refractory primary mediastinal large B-cell lymphoma.

Not available.

Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported the results of a randomized phase II study in patients with newly diagnosed primary CNS lymphoma (age 18-60 years). Patients were treated with high-dose methotrexate-based induction chemotherapy followed by whole-brain radiotherapy (WBRT) or high-dose chemotherapy (thiotepa-busulfan-cyclophosphamide) with autologous stem-cell transplantation (ASCT). The median follow-up was 33 months. In this report, we provide long-term data (median follow-up, 8 years) regarding the outcomes and toxicities. Fifty-three and 44 patients received induction chemotherapy followed by WBRT or ASCT, respectively. Their 8-year event-free survival from random assignment was 67% and 39% in the ASCT and WBRT arms, respectively (P = .03), with a significantly lower risk of relapse after ASCT (hazard ratio, 0.13; P < .001). One third of patients who relapsed after WBRT were alive after salvage treatment. Five and four patients died of ASCT and WBRT-related toxicities, respectively. The 8-year overall survival was 69% and 65% in the ASCT and WBRT arms, respectively (not significant). Balance (52% v 10%, P ≤ 0.001) and neurocognition (64% v 13%, P < .001) significantly deteriorated after WBRT compared with ASCT during the follow-up. This study shows that 40 Gy WBRT should be avoided in first-line treatment because of its neurotoxicity and suboptimal efficacy in reducing relapses while ASCT appears to be highly efficient in preventing relapses.

Eltrombopag for myelodysplastic syndromes or chronic myelomonocytic leukaemia with no excess blasts and thrombocytopenia: a French multicentre retrospective real-life study.

Despite a moderate prevalence in low-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), thrombocytopenia remains a risk of severe bleeding and therapeutic options are still limited. There are only a few studies with eltrombopag (ELT), a thrombopoietin receptor agonist, in those patients. In this retrospective multicentre study, ELT was used in 50 patients with MDS and 11 with CMML, with no excess of marrow blasts and platelet counts of <50 × 109 /l in a 'real-life' situation. Platelet response occurred in 47 (77%) patients. The median (range) duration of response was 8 (0-69) months. None of the eight still responders who discontinued ELT had relapsed, at a median (range) of 16 (6-23) months after ELT discontinuation. Although 36% of the patients were anti-coagulated or anti-aggregated only 10% of patients had Grade ≥3 bleeding events. Thrombotic events were observed in six (10%) patients, who all but one had a medical history of arterial or venous thrombosis. Progression to acute myeloid leukaemia occurred in four (7%) patients. In this first 'real-life' study, ELT was effective and generally well tolerated in patients with MDS/CMML without excess blasts.

Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients 60 Years of Age and Younger: Results of the Intergroup ANOCEF-GOELAMS Randomized Phase II PRECIS Study.

PURPOSE: To determine the efficacy and toxicity of chemoimmunotherapy followed by either whole-brain radiotherapy (WBRT) or intensive chemotherapy and autologous stem-cell transplantation (ASCT) as a first-line treatment of primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: Immunocompetent patients (18 to 60 years of age) with untreated PCNSL were randomly assigned to receive WBRT or ASCT as consolidation treatment after induction chemotherapy consisting of two cycles of R-MBVP (rituximab 375 mg/m2 day (D) 1, methotrexate 3 g/m2 D1; D15, VP16 100 mg/m2 D2, BCNU 100 mg/m2 D3, prednisone 60 mg/kg/d D1-D5) followed by two cycles of R-AraC (rituximab 375 mg/m2 D1, cytarabine 3 g/m2 D1 to D2). Intensive chemotherapy consisted of thiotepa (250 mg/m2/d D9; D8; D7), busulfan (8 mg/kg D6 through D4), and cyclophosphamide (60 mg/kg/d D3; D2). WBRT delivered 40 Gy (2 Gy/fraction). The primary end point was 2-year progression-free survival. Cognitive outcome was the main secondary end point. Analysis was intention to treat in a noncomparative phase II trial. RESULTS: Between October 2008 and February 2014, 140 patients were recruited from 23 French centers. Both WBRT and ASCT met the predetermined threshold (among the first 38 patients in each group, at least 24 patients were alive and disease free at 2 years). The 2-year progression-free survival rates were 63% (95% CI, 49% to 81%) and 87% (95% CI, 77% to 98%) in the WBRT and ASCT arms, respectively. Toxicity deaths were recorded in one and five patients after WBRT and ASCT, respectively. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. CONCLUSION: WBRT and ASCT are effective consolidation treatments for patients with PCNSL who are 60 years of age and younger. The efficacy end points tended to favor the ASCT arm. The specific risk of each procedure should be considered.

Prevalence of monoclonal gammopathy in HIV patients in 2014.

INTRODUCTION: In non-HIV patients, Monoclonal Gammopathy of Undetermined Significance (MGUS) is associated with an increased risk of subsequent development of haematologic malignancies, especially multiple myeloma (MM) and it has been recently demonstrated that MM is always preceded by a MGUS phase. A higher prevalence of MGUS and MM has been observed in HIV patients compared to the general population. Nevertheless, it has been shown that MGUS in the context of HIV can disappear with antiretroviral therapy (ART). So, measuring MGUS prevalence in HIV patients in the recent period appears of special interest. MATERIALS AND METHODS: From January to June 2014, in each out-patient seen in our unit, a serum protein electrophoresis was performed. RESULTS: A total of 393 patients were screened. Eight patients with HIV2 and one patient with HIV1+HIV2 infection were excluded. Finally, 383 patients (173 female, 210 male) with HIV1 infection were analyzed. Characteristics of patients were as follows: median age 42.2 years (19.1-79.1), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection 47 (18.8%), median CD4 610 (2-1758), CD8 793 (113-4010), presence of a past AIDS event for 88 patients (23%). Median time with HIV infection was 11 years (0-30). Three hundred fifty-nine patients (93.7%) were on ART for a median duration of 105 months (0-287). For 320 patients (83.6%), viral load was below 50 viral copies/ml. Twelve cases of MGUS (3.1%) were observed: IgG Kappa (five cases), IgG Lambda (five cases), biclonal with two IgG Kappa (one case) and in one case, three monoclonal immunoglobulins were observed (IgG Kappa×2+IgG Lambda). The monoclonal immunoglobulin's level was low and below 1 g/l in all cases except two (2.1 and 11.6 g/l). No factor was found to be predictive of the presence of MGUS in particular age, CD4, HBV/HCV co-infection, viral load or ART. CONCLUSIONS: In the context of modern ART, the prevalence of MGUS remains above those observed in the general population. Even if the level of monoclonal spike observed in our cohort is generally low, an excess risk of subsequent development of MM could be present. Nevertheless, a prospective follow-up of HIV patients with MGUS is necessary to determine this risk.

MELISSE, a large multicentric observational study to determine risk factors of venous thromboembolism in patients with multiple myeloma treated with immunomodulatory drugs.

Immunomodulatory drugs (IMiDs) are associated with an increased risk of venous thromboembolism (VTE) in multiple myeloma (MM) patients. We designed MELISSE, a multicentre prospective observational study, to evaluate VTE incidence and identify risk factors in IMiDs-treated MM. Our objective was to determine the real-life practice of VTE prophylaxis strategy. A total of 524 MM patients were included, and we planned to collect information at baseline, at four and at 12 months, on MM therapy, on VTE risk factors and management. VTE incidence was 7% (n=31), including 2.5% pulmonary embolism (PE) (n=11), similar at four or 12 months. VTE was observed at all risk assessment levels, although the increased risk assessment level correlated to a lower rate of VTE, maybe due to the implemented thromboprophylaxis strategy. VTE occurred in 7% on aspirin vs 3% on low-molecular-weight heparin (LMWH) prophylaxis, and none on vitamin K antagonists (VKA). New risk factors for VTE in IMiDs-treated MM were identified. In conclusion, VTE prophylaxis is compulsory in IMiDs-treated MM, based on individualised VTE risk assessment. Anticoagulation prophylaxis with LMWH should clearly be prioritised in MM patients with high VTE risk, along with VKA. Further prospective studies will identify most relevant VTE risk factors in IMiDs-treated MM to select accurately which MM patients should receive LMWH prophylaxis and for which duration to optimise VTE risk reduction.

High-output cardiac failure revealing primary plasma cell leukemia.

High-output cardiac failure in multiple myeloma (MM) is related to arteriovenous shunting in bone infiltrate disease. We describe such a complication in a patient with primary plasma cell leukemia (pPCL) without bone disease. We review the mechanisms that could be involved. As previously described, traditional cardiac failure therapy is not effective. pPCL therapy should not be delayed.

Anaplastic Large Cell Lymphoma Occurring in an HIV-Positive Patient.

Cases of anaplastic large-cell lymphoma (ALCL) of T phenotype are sparse in the setting of HIV patients. We report herein a case of T-ALCL, with an advanced stage, pulmonary involvement, high HIV viral load, and low CD4 level. Anaplastic lymphoma kinase (ALK) protein expression was negative. Anthracyclin-based chemotherapy was unsuccessful. The literature review was performed focusing on incidence, clinical characteristics, prognosis, and physiopathology of ALCL in HIV patients. More data are needed to improve the knowledge of such cases and to define a better treatment approach.

Detection of Aspergillus galactomannan antigenemia to determine biological and clinical implications of beta-lactam treatments.

Detection of Aspergillus galactomannan (GM) in serum with the Platelia Aspergillus enzyme immunoassay (EIA) is useful for diagnosing invasive aspergillosis. From May 2003 to November 2004, 65 patients who did not develop aspergillosis had at least two positive sera while receiving a beta-lactam treatment (GM index [GMI], >or=0.5). Of the 69 treatment episodes scored, 41 consisted of a beta-lactam other than piperacillin-tazobactam (n=29), namely, amoxicillin-clavulanate (n=25), amoxicillin (n=10), ampicillin (n=3), or phenoxymethylpenicillin (n=2). In all cases, antigenemia became negative 24 h to 120 h upon stopping the antibiotic. Monitoring of 35 patients, including 26 with hematological malignancies, revealed three antigenemia kinetic patterns: each was observed with any drug regimen and consisted of a persistent GMI of >2.0 (65.7%), >0.5, and

NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect.

Natural killer (NK) cell alloreactivity is reported to mediate strong GvL (graft versus leukemia) effect in patients after haploidentical stem-cell transplantation (SCT) for acute myeloid leukemia (AML). Because subsequent immune reconstitution remains a major concern, we studied NK-cell recovery in 10 patients with AML who received haplomismatched SC transplants, among whom no GvL effect was observed, despite the mismatched immunoglobulin-like receptor (KIR) ligand in the GvH direction for 8 of 10 patients. NK cells generated after SCT exhibited an immature phenotype: the cytotoxic CD3- CD56(dim) subset was small, expression of KIRs and NKp30 was reduced, while CD94/NKG2A expression was increased. This phenotype was associated to in vitro lower levels of cytotoxicity against a K562 cell line and against primary mismatched AML blasts than donor samples. This impaired lysis was correlated with CD94/NKG2A expression in NK cells. Blockading CD94/NKG2A restored lysis against the AML blasts, which all expressed HLA-E, the ligand for CD94/NKG2A. Our present study allows a better understanding of the NK-cell differentiation after SCT. These results revealed that the NK cells generated after haplomismatched SCT are blocked at an immature state characterized by specific phenotypic features and impaired functioning, having potential impact for immune responsiveness and transplantation outcome.

Small-bowel infarction from disseminated aspergillosis.

INTRODUCTION: Despite the use of new, effective drugs, the disseminated invasive aspergillosis often remains lethal in neutropenic patients. Diagnosis is difficult because early symptoms are nonspecific. New tools could help in diagnosis and lead to early surgery when needed. METHODS: A neutropenic patient developed an acute abdomen. CT findings were a diffuse, small-bowel distention with a thickened, distal, ileum wall. Emergency surgery was performed with resection and immediate anastomosis of the distal ileum. Pathology of the small bowel showed a wall necrosis and invasion by Aspergillus fumigatus. RESULTS: The postoperative course was uneventful except for persisting diarrhea secondary to a coexistent infection with Clostridium difficile. Aspergillus antigene in serum was positive, whereas neither pulmonary nor central nervous system aspergillosis was observed on CT scan. CONCLUSIONS: This diagnosis should be considered when neutropenic patients show abdominal pain and distention with fever. Repetition of Aspergillus antigenemia, search for others aspergillosis localizations, CT scan, and colonoscopy with biopsies should be performed until diagnosis allows the administration of early antifungal therapy.

A case of multicentric Castleman's disease associated with advanced systemic amyloidosis treated with chemotherapy and anti-CD20 monoclonal antibody.

Multicentric Castleman's disease (MCD) is a rare systemic lymphoproliferative disorder with too few patient series reported in the literature to have a clear idea about the etiology, outcome and the best treatment available. Systemic reactive amyloidosis is a very rare complication of MCD and its presence worsens the prognosis. We report a case of a 28-year-old patient with plasma-cell type, human immunodeficiency virus (HIV)-negative and human herpesvirus-8 (HHV-8)-negative MCD who responded to treatment with chemotherapy and the anti-CD20 monoclonal antibody, rituximab. Anti-CD20 therapy could be an interesting adjunctive treatment in MCD.