Bendamustine and rituximab combination in the management of chronic lymphocytic leukemia‐associated autoimmune hemolytic anemia: A multicentric retrospective study of the French CLL intergroup (GCFLLC/MW and GOELAMS)

Quinquenel, Anne; Willekens, Christophe; Dupuis, Jehan; Royer, Bruno; Ysebaert, Loïc; Guibert, Sophie de; Michallet, Anne‐Sophie; Feugier, Pierre; Guièze, Romain; Lévy, Vincent; Delmer, Alain

doi:10.1002/ajh.23909

Cited by 39 publications

(35 citation statements)

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“…If additional CLL treatment is needed, we prefer rituximab/cyclophosphamide/ dexamethasone, bendamustine/rituximab, or novel signal inhibitors because of their safety in this setting. [56][57][58][59] These 2 chemotherapy combination regimens have been shown to effectively treat steroid-refractory AIHA. In most (.80%) of the cases, there was sustained control of hemolysis and CLL.…”

Section: 44mentioning

confidence: 99%

“…In most (.80%) of the cases, there was sustained control of hemolysis and CLL. 58,59 Among those who were receiving AIHA treatment, the initiation of ibrutinib frequently allowed discontinuation of AIHA treatment within 5 months. 47 Five drugs have been recently approved for use in CLL: ibrutinib, idelalisib, obinutuzumab, ofatumumab, and venetoclax.…”

Section: 44mentioning

confidence: 99%

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How I treat autoimmune hemolytic anemia

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Winters

Kay³

2017

Blood

156

113

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Autoimmune hemolytic anemia (AIHA) is an uncommon entity that presents diagnostic, prognostic, and therapeutic dilemmas despite being a well-recognized entity for over 150 years. This is because of significant differences in the rates of hemolysis and associated diseases and because there is considerable clinical heterogeneity. In addition, there is a lack of clinical trials required to refine and update standardized and evidence-based therapeutic approaches. To aid the clinician in AIHA management, we present four vignettes that represent and highlight distinct clinical presentations with separate diagnostic and therapeutic pathways that we use in our clinical practice setting. We also review the parameters present in diagnostic testing that allow for prognostic insight and present algorithms for both diagnosis and treatment of the AIHA patient in diverse situations. This is done in the hope that this review may offer guidance in regard to personalized therapy recommendations. A section is included for the diagnosis of suspected AIHA with negative test results, a relatively infrequent but challenging situation, in order to assist in the overall evaluation spectrum for these patients. (Blood. 2017; 129(22):2971-2979

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Section: 44mentioning

confidence: 99%

Section: 44mentioning

confidence: 99%

How I treat autoimmune hemolytic anemia

Go¹,

Winters

Kay³

2017

Blood

156

113

View full text Add to dashboard Cite

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“…Therapy with BR has been shown to be a safe and effective therapy in patients with AIHA secondary to CLL, refractory to other therapies, who also required control of their progressive CLL. In a study of 26 CLL patients treated with BR, 42 the overall response rate was 81% for AIHA and 77% for CLL with a median time to next treatment of 28 months for AIHA and 26 months for CLL. In a study of 8 CLL patients who had steroid refractory AIHA, 43 the combination of rituximab-cyclophosphamide-dexamethasone (RCD), was shown to have an overall response rate of 89% and a complete response rate of 83%.…”

Section: Autoimmune Hemolytic Anemiamentioning

confidence: 99%

A Concise Review of Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

Tsang

2017

Curr Hematol Malig Rep

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Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune complications such as autoimmune hemolytic anemia, immune thrombocytopenia, pure red cell aplasia and autoimmune granulocytopenia. It is critical to diagnose cytopenias from these secondary complications of CLL accurately, since prognosis and therapy are substantially different from patients who have cytopenias due to extensive bone marrow infiltration by CLL. The pathogenesis of autoimmune cytopenias in CLL is complex; and involves antigen presentation by CLL cells to polyclonal B-cells resulting in production of autoantibody and alteration of the T-cell milieu tilting the balance in favor of an autoimmune response. Traditional therapy of autoimmune complications in CLL consists of immunosuppression with corticosteroids and/or anti-CD20 monoclonal antibodies. In patients who have a suboptimal response, treating the underlying CLL is generally effective in ameliorating secondary cytopenias. Although novel oral therapies such as ibrutinib, idelalisib and venetoclax have been shown to be extremely effective in the management of CLL; prospective data from larger numbers of patients with longer follow-up are needed prior to recommending their routine use in the management of autoimmune cytopenias in CLL.

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“…In this context, we investigated the feasibility of using the bifunctional mechlorethamine derivative bendamustine (BEN), an active alkylator and purine analogue, following h-BMT (Hartmann & Zimmer, 1972;Tageja & Nagi, 2010). BEN has been used effectively against lymphomas (Corazzelli et al, 2013;Derenzini et al, 2014;Kahl et al, 2010;Rigacci et al, 2012;Robinson et al, 2008), chronic lymphocytic leukaemia (Bergmann et al, 2005;Quinquenel et al, 2015) and, more recently, as conditioning for allogeneic HCT (Khouri et al, 2014). This agent has also been applied as pre-treatment for chimeric antigen receptor T-cell therapy of leukaemias, as it induces a sustained lymphodepletion earlier than other agents (Kalos et al, 2011).…”

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confidence: 99%

Post‐transplant bendamustine reduces GvHD while preserving GvL in experimental haploidentical bone marrow transplantation

et al. 2016

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Advances in haploidentical bone marrow transplantation (h-BMT) have drastically broadened the treatment options for patients requiring BMT. The possibility of significantly reducing the complications resulting from graft-versus-host disease (GvHD) with the administration of post-transplant cyclophosphamide (PT-CY) has substantially improved the efficacy and applicability of T cell-replete h-BMT. However, higher frequency of disease recurrence remains a major challenge in h-BMT with PT-CY. There is a critical need to identify novel strategies to prevent GvHD while sparing the graft-versus-leukaemia (GvL) effect in h-BMT. To this end, we evaluated the impact of bendamustine (BEN), given post-transplant, on GvHD and GvL using clinically relevant murine h-BMT models. We provide results indicating that post-transplant bendamustine (PT-BEN) alleviates GvHD, significantly improving survival, while preserving engraftment and GvL effects. We further document that PT-BEN can mitigate GvHD even in the absence of Treg. Our results also indicate that PT-BEN is less myelosuppressive than PT-CY, significantly increasing the number and proportion of CD11b+Gr-1hi cells, while decreasing lymphoid cells. In vitro we observed that BEN enhances the suppressive function of myeloid-derived suppressor cells (MDSCs) while impairing the proliferation of T- and B-cells. These results advocate for the consideration of PT-BEN as a new therapeutic platform for clinical implementation in h-BMT.

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Bendamustine and rituximab combination in the management of chronic lymphocytic leukemia‐associated autoimmune hemolytic anemia: A multicentric retrospective study of the French CLL intergroup (GCFLLC/MW and GOELAMS)

Cited by 39 publications

References 20 publications

How I treat autoimmune hemolytic anemia

How I treat autoimmune hemolytic anemia

A Concise Review of Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

Post‐transplant bendamustine reduces GvHD while preserving GvL in experimental haploidentical bone marrow transplantation

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