Rituximab maintenance versus observation alone in patients with chronic lymphocytic leukaemia who respond to first-line or second-line rituximab-containing chemoimmunotherapy: final results of the AGMT CLL-8a Mabtenance randomised trial.

BACKGROUND: In many patients with chronic lymphocytic leukaemia requiring treatment, induction therapy with rituximab plus chemotherapy improves outcomes compared with chemotherapy alone. In this study we aimed to investigate the potential of rituximab maintenance therapy to prolong disease control in patients who respond to rituximab-containing induction regimens. METHODS: In this randomised, international, multicentre, open-label, phase 3 clinical trial, we enrolled patients who had achieved a complete response (CR), CR with incomplete bone marrow recovery (CRi), or partial response (PR) to first-line or second-line rituximab-containing chemoimmunotherapy and randomly assigned them in a 1:1 ratio (central block randomisation in the electronic case report form system) to either intravenous rituximab 375 mg/m(2) every 3 months, or observation alone, for 2 years. Stratification was by country, line of treatment, type of chemotherapy added to the rituximab backbone, and degree of remission following induction. The primary endpoint was progression-free survival. Efficacy analysis was done in the intention-to-treat population. This is the final, event-triggered analysis. Final analysis was triggered by the occurrence of 92 events. This trial is registered with ClinicalTrials.gov, number NCT01118234. FINDINGS: Between April 1, 2010, and Dec 23, 2013, 134 patients were randomised to rituximab and 129 to observation alone. Median observation times were 33·4 months (IQR 25·7-42·8) for the rituximab group and 34·0 months (25·4-41·9) for the observation group. Progression-free survival was significantly longer in the rituximab maintenance group (47·0 months, IQR 28·5-incalculable) than with observation alone (35·5 months, 95% CI 25·7-46·3; hazard ratio [HR] 0·50, 95% CI 0·33-0·75, p=0·00077). The incidence of grade 3-4 haematological toxicities other than neutropenia was similar in the two treatment groups. Grade 3-4 neutropenia occurred in 28 (21%) patients in the rituximab group and 14 (11%) patients in the observation group. Apart from neutropenia, the most common grade 3-4 adverse events were upper (five vs one [1%] patient in the observation group) and lower (three [2%] vs one [1%]) respiratory tract infection, pneumonia (nine [7%] vs two [2%]), thrombopenia (four [3%] vs four [3%]), neoplasms (five [4%] vs four [3%]), and eye disorders (four [3%] vs two [2%]). The overall incidence of infections of all grades was higher among rituximab recipients (88 [66%] vs 65 [50%]). INTERPRETATION: Rituximab maintenance therapy prolongs progression-free survival in patients achieving at least a PR to induction with rituximab plus chemotherapy, and the treatment is well tolerated overall. Although it is associated with an increase in infections, there is no excess in infection mortality, suggesting that remission maintenance with rituximab is an effective and safe option in the management of chronic lymphocytic leukaemia in early treatment phases. FUNDING: Arbeitsgemeinschaft Medikamentöse Tumortherapie gemeinnützige GmbH (AGMT), Roche.

Pact with the devil: alemtuzumab therapy, immune suppression and infectious complications in chronic lymphocytic leukemia.

Infectious complications are an important cause of hospitalization in patients diagnosed with chronic lymphocytic leukemia. The pathogenesis of infection is complex, involving both disease-induced and treatment-related immune depression. During the last decade, the management of chronic lymphocytic leukemia (CLL) has been redefined by the approval of monoclonal antibody-based treatment, which resulted in improved therapeutic responses. Nonetheless, the profound lymphopenia induced by monoclonal agents was accompanied by increased incidence of infections caused by a new spectrum of opportunistic microorganisms. We report the case of a patient with hypercellular CLL who received Alemtuzumab as first line therapy and obtained a satisfactory therapeutic response, but developed subsequent atypical infectious complications.

Flow cytometry-based quantification of cytokine levels in AML patients plasma and cell culture supernatants.

AIM: Bone marrow stromal cells (BMSCs) have been found to support leukemic cell survival; however, the mechanisms responsible are far from being elucidated yet. The main aim of the current study is to identify particular cytokine/chemokine patterns of acute myeloid leukemia (AML) cells, and, on a longer term, to correlate them with the patient outcome and response to therapy. Therefore, the influence of BMSCs on in vitro modulation of cytokine secretion (IL-1beta, TNF-alpha, IL-10, IFN-gamma, IL-4, IL-5, and IL-2) by AML cells as well as the AML cells supportive capacity of BMSCs-derived soluble factors was investigated. MATERIAL AND METHODS: With this purpose, we used an in vitro experimental model consisting in the evaluation of the effect of BMSC confluent layers-conditioning medium (BMSC-CM) on M4/5 AML cell cultures. RESULTS: Our results show that BMSC-CM from both AML patients and healthy subjects conferred a substantial beneficial effect on AML cells throughout the culture (p=0.0002 and 0.0020 respectively at 24 hours and p=0,0013 and 0,0030 respectively at 72 hours), with a temporary increase in AML cell viability conferred by BM plasma from AML patients. Significant differences were observed with respect to IL1 b secretion which was upregulated in AML cell cultures both after 24 and 72 hours following the addition of AML-BMSC-CM, in contrast to control-BMSC-CM. CONCLUSION: Our results suggest the contribution of BMSCs from AML patients to the generation of particular factors which may be key players involved in the in vivo maintenance of the malignant clone.

Disseminated infection due to Candida guilliermondii in a patient with AML(M4). Case study.

UNLABELLED: A 43-year-old patient admitted with acute myelogenous leukemia, developed bronchopneumonia and sepsis during profound neutropenia. Fever and pulmonary infiltrates did not improve by using empiric antibacterial therapy (Cefoperazona-Sulbactam, Trimethoprim-Sulphametoxazol). Blood and sputum culture were performed and patient received Voriconazol. Both cultures, from blood and sputum, yielded Candida guilliermondii after 48 hours of incubations. The isolates have the same biochemical and antimicrobial spectrum and were susceptible to Amphotericin B and Fluconazole. After a few days of therapy with Voriconazol, fever disappeared and the clinical state of patient was improved. A culture from pharyngeal swab, performed after 11 days, yielded the same microorganism. CONCLUSIONS: (1) The emergence of less common, but medically important fungal pathogens, including Candida guilliermondii, contributes to the rate of morbidity and mortality, especially in the increasingly expanding population of immunocompromised patients. (2) We consider that the oropharyngeal colonization with Candida guilliermondii and profound neutropenia predispose our patient to develop bronchopneumonia and candidemia.

[Disseminated infections due to Scedosporium apiospermum in a patient with anaplastic large cell lymphoma. A case study]. / Infectie diseminata cu Scedosporium apiospermum la un pacient cu limfom anaplastic tip T cu celule mari. Prezentare de caz.

A 42-year-old man was diagnosed with hepatosplenic T-cell lymphoma in November 2003. Remission was incompletely achieved despite 10 courses of chemotherapy. He developed fever (38.5-39 degrees C), chills, cough and morning expectoration after the 61 courses of chemotherapy. During this period, an ultrasound of the abdomen showed multiple hypodense lesions of the liver. Culture of the sputum yielded Scedosporium apiospermum. Fungal cultures from blood remained negative. The patient was treated with voriconazol. After one month from therapy, an ultrasound examination showed decreasing of hypodense lesions of the liver, and no further lesions appeared. Based on significant improvement of liver lesions with voriconazole therapy, we proposed the diagnostic "probable" disseminated infections due to S.apiospermum.