Key Points Routine staging by PET-CT identifies all clinically relevant marrow involvement by DLBCL. Cases with marrow involvement identified by PET-CT have PFS and overall survival similar to stage IV cases without marrow involvement.

Relapse remains the most common cause of treatment failure for patients with acute myeloid leukemia (AML) who undergo allogeneic stem cell transplantation (alloSCT), and carries a grave prognosis. Multiple studies have identified the presence of measurable residual disease (MRD) assessed by flow cytometry before alloSCT as a strong predictor of relapse, but it is not clear how these findings apply to patients who test positive in molecular MRD assays, which have far greater sensitivity. We analyzed pretransplant blood and bone marrow samples by reverse-transcription polymerase chain reaction in 107 patients with NPM1-mutant AML enrolled in the UK National Cancer Research Institute AML17 study. After a median follow-up of 4.9 years, patients with negative, low (<200 copies per 105ABL in the peripheral blood and <1000 copies in the bone marrow aspirate), and high levels of MRD had an estimated 2-year overall survival (2y-OS) of 83%, 63%, and 13%, respectively (P < .0001). Focusing on patients with low-level MRD before alloSCT, those with FLT3 internal tandem duplications(ITDs) had significantly poorer outcome (hazard ratio [HR], 6.14; P = .01). Combining these variables was highly prognostic, dividing patients into 2 groups with 2y-OS of 17% and 82% (HR, 13.2; P < .0001). T-depletion was associated with significantly reduced survival both in the entire cohort (2y-OS, 56% vs 96%; HR, 3.24; P = .0005) and in MRD-positive patients (2y-OS, 34% vs 100%; HR, 3.78; P = .003), but there was no significant effect of either conditioning regimen or donor source on outcome. Registered at ISRCTN (http://www.isrctn.com/ISRCTN55675535).

A key predictor for the success of gene-modified T cell therapies for cancer is the persistence of transferred cells in the patient. The propensity of less differentiated memory T cells to expand and survive efficiently has therefore made them attractive candidates for clinical application. We hypothesized that redirecting T cells to specialized niches in the BM that support memory differentiation would confer increased therapeutic efficacy. We show that overexpression of chemokine receptor CXCR4 in CD8+ T cells (TCXCR4) enhanced their migration toward vascular-associated CXCL12+ cells in the BM and increased their local engraftment. Increased access of TCXCR4 to the BM microenvironment induced IL-15–dependent homeostatic expansion and promoted the differentiation of memory precursor–like cells with low expression of programmed death-1, resistance to apoptosis, and a heightened capacity to generate polyfunctional cytokine-producing effector cells. Following transfer to lymphoma-bearing mice, TCXCR4 showed a greater capacity for effector expansion and better tumor protection, the latter being independent of changes in trafficking to the tumor bed or local out-competition of regulatory T cells. Thus, redirected homing of T cells to the BM confers increased memory differentiation and antitumor immunity, suggesting an innovative solution to increase the persistence and functions of therapeutic T cells.

Conflict of interest: COI declared -see note COI notes: V.M. received research grants from MSD/ Gilead and speakership from MSD, Gilead, Pfizer, Novartis, Jazz, Incyte. E.T. declares advisory boards for Celgene, Gilead/Kite, Jazz, Novartis, Pfizer and MSD, speaker fees for Gilead/Kite, Janssen, Jazz, Novartis and Pfizer and consultancy for educational materials for Gilead/Kite. A.P. declares advisory board for MSD. R.L. received educational grants and speaker fees for MSD, Chugai Pharma, Astellas, Gilead, Sanofi. E.N. declares advisory boards for Kite/Gilead, Novartis, BMS/Celgene, Pfizer and conference support for Kite/Gilead, Novartis and speaker fees for Kite/Gilead. J.A.S. declares honoraria for educational events supported by Jazz, Mallinckrodt, Gilead, Janssen, and Actelion, advisory board participation for Medac and IDMC membership for a Kiadis Pharma supported clinical trial, none of which are directly related to this study. E.H.

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SummaryA 74-year-old woman with a history of psoriatic arthritis was referred to the Hospital for Tropical Diseases following investigation of a skin lesion that had failed to heal after a visit to Malta 2 years previously. Skin biopsy had revealed invasion of Leishmania amastigotes. She reported a recent history of weight loss, dry cough and dyspnoea, and was investigated for pancytopenia and hepatosplenomegaly.Bone marrow biopsy confirmed the diagnosis of visceral leishmaniasis and she responded well to treatment with intravenous liposomal amphotericin B. Recent rheumatological treatment with adalimumab, a monoclonal antibody to tumour necrosis factor α, was thought to be the factor responsible for causing the cutaneous lesion to become disseminated. This case highlights an unexpected adverse effect of novel immunosuppressants. As the use of biologics becomes widespread, there is an increasing need for clinical surveillance. BACKGROUND

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