Hairy cell leukemia 2018: Update on diagnosis, risk-stratification, and treatment
AMERICAN JOURNAL OF HEMATOLOGY
Authors: Troussard, Xavier; Cornet, Edouard
Abstract
Disease overviewHairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders, characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment. DiagnosisDiagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation. Risk stratificationProgression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood and the immunoglobulin heavy chain variable region gene mutational status. VH4-34 positive HCL cases are associated with poor prognosis Risk adapted therapyPurine analogs (PNA) are indicated in symptomatic first line HCL patients. The use of PNA followed by rituximab represents an alternative option. Management of progressive or refractory diseaseIt is based on the use of BRAF inhibitors associated or not with MEK inhibitors, recombinant immunoconjugates targeting CD22 or BCR inhibitors.
How should we treat a patient with relapsed Ph-negative B-ALL and what novel approaches are being investigated?
BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
Authors: Goekbuget, Nicola
Abstract
Despite significant improvements in outcome of newly diagnosed B-precursor ALL, the results in relapsed or refractory adult ALL are overall poor. Large retrospective studies revealed significant differences in terms of outcome, with particularly poor response rates in early or refractory relapses, whereas late relapses usually respond very well to repeated standard induction. Particularly new immunotherapy compounds like the CD19 bispecific antibody Blinatumomab and the conjugated CD22 antibody Inotuzumab yielded promising response rates compared to standard therapies in randomised trials. Long-term survival is however still poor. The optimal use of these compounds remains to be defined. Chimeric antigen receptor T-cells are another promising treatment approach and multicenter clinical trials in adult ALL are awaited. For selected patients molecular directed therapies may have a role in relapsed ALL; standard diagnostic algorithms need to be defined. One of the major challenges is to define the role of stem cell transplantation after relapse. Whereas this procedure appears to be the only chance for cure, the mortality and relapse rate are still high and optimisation is urgently needed. Future strategies include optimised use of new compounds as part of combination regimens and the earlier treatment of upcoming relapse in the situation of persistent or recurrent minimal residual disease. (C) 2017 Elsevier Ltd. All rights reserved.