Infections are the most common and significant cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The presence of neutropenia and mucosal damage are the leading risk factors in the early pre-engraftment phase. In the early post-engraftment phase, graft versus host disease (GvHD) induced infection risk is increased in addition to catheter related infections. In the late phase, in which reconstitution of cellular and humoral immunity continues, as well as the pathogens seen during the early post-engraftment phase, varicella-zoster virus and encapsulated bacterial infections due to impaired opsonization are observed. An appropriate vaccination schedule following the cessation of immunosuppressive treatment after transplantation, intravenous immunoglobulin administration, and antimicrobial prophylaxis with penicillin or macrolide antibiotics during immunosuppressive treatment for GvHD might decrease the risk of bacterial infections. Older age, severe mucositis due to toxicity of chemotherapy, gastrointestinal tract colonization, prolonged neutropenia, unrelated donor and cord blood originated transplantations, acute and chronic GvHD are among the most indicative clinical risk factors for invasive fungal infections. Mold-active anti-fungal prophylaxis is suggested regardless of the period of transplantation among high risk patients. The novel serological methods, including Aspergillus galactomannan antigen and beta-D-glucan detection and computed tomography are useful in surveillance. Infections due to adenovirus, influenza and respiratory syncytial virus are encountered in all phases after allo-HSCT, including pre-engraftment, early post-engraftment and late phases. Infections due to herpes simplex virus-1 and -2 are mostly seen during the pre-engraftment phase, whereas, infections due to cytomegalovirus and human herpes virus-6 are seen in the early post-engraftment phase and Epstein-Barr virus and varicella-zoster virus infections often after +100th day. In order to prevent mortality and morbidity of infections after allo-HSCT, the recipients should be carefully followed-up with appropriate prophylactic measures in the post-transplant period.

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty-eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (p<0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and >1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (p<0.001). Neurological manifestations, not considered chemotherapy-related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy.

Chimeric antigen receptor (CAR) T cell therapy for the treatment of acute myeloid leukemia (AML) has the risk of toxicity to normal myeloid cells. CD7 is expressed by the leukemic blasts and malignant progenitor cells of approximately 30% of AML patients but is absent on normal myeloid and erythroid cells. Since CD7 expression by malignant blasts is also linked with chemoresistance and poor outcomes, targeting this antigen may be beneficial for this subset of AML patients. Here, we show that expression of a CD7-directed CAR in CD7 gene-edited (CD7 KO ) T cells effectively eliminates CD7 + AML cell lines, primary CD7 + AML, and colony-forming cells but spares myeloid and erythroid progenitor cells and their progeny. In a xenograft model, CD7 CAR T cells protect mice against systemic leukemia, prolonging survival. Our results support the feasibility of using CD7 KO CD7 CAR T cells for the non-myeloablative treatment of CD7 + AML.