Rituximab as treatment for minimal residual disease in hairy cell leukaemia: extended follow‐up

Cervetti, Giulia; Galimberti, Sara; Andreazzoli, Francesca; Fazzi, Rita; Cecconi, Nadia; Caracciolo, F; Petrini, Mario

doi:10.1111/j.1365-2141.2008.07333.x

Cited by 30 publications

(27 citation statements)

References 10 publications

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“…Moreover, results are difficult to interpret because of the heterogeneity of the techniques and samples used for each patient. The low rate of MRD negativity we observe after rituximab (two of nine patients) may also be due to the fact that MRD evaluation was often performed quite early after treatment, whereas previously published data have shown that molecular responses increase over time and are still quite low at 2 and even 6 months [19,14].…”

Section: Discussionmentioning

confidence: 68%

“…Whereas the largest series published to date concerns the use of rituximab in combination with PA for frontline therapy of HCL [14,15], this situation represents only 5 of the 49 treatments reported in our study, with an excellent treatment outcome (100 % CHR). Most of our patients were treated at relapse, after multiple courses of therapy and a median time of more than 6 years since HCL diagnosis.…”

Section: Discussionmentioning

confidence: 75%

“…These encouraging results have led to combine rituximab with PA, both in previously untreated and in relapsed patients. As frontline therapy, combination with cladribine provided an impressive 100 % response rate in two separate cohorts that included a total of 63 patients [14,15]. Moreover, molecular responses were obtained in 70 % of these patients.…”

Section: Introductionmentioning

confidence: 99%

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Rituximab therapy for hairy cell leukemia: a retrospective study of 41 cases

et al. 2014

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The purine analogs (PAs) cladribine and pentostatin have transformed the prognosis of hairy cell leukemia (HCL). However, some patients still relapse after PAs, or fail to reach an optimal response, and new agents are needed to further improve treatment outcome. We retrospectively studied 41 HCL patients from 10 centers in France and Belgium, who received 49 treatment courses with the anti-CD20 monoclonal antibody rituximab. Most of the patients were treated at relapse (84 % of cases) and rituximab was combined to a PA in 41 % of cases. Overall, response rate is 90 % including 71 % complete hematologic responses (CHRs). Frontline treatment, combination therapy, and absolute neutrophil count were associated with response in multivariate analysis. Three-year relapse-free and overall survivals are 68 and 90 %, respectively. When combined to a PA, rituximab yields a 100 % response rate, even beyond frontline therapy. In contrast, response rate is only 82 % (59 % CHR) when rituximab is used alone. In this latter setting, relapse rate is 56 % and median time to relapse is 17.5 months. All eight patients who were treated two times with the antibody responded again to retreatment. We confirm the high efficacy of the combination rituximab + PA. However, when rituximab is used as monotherapy, response rate is lower and the high relapse rate is a concern. Prospective clinical trials are needed to confirm the superiority of the combination rituximab + PA over PA alone, both as frontline therapy and at relapse.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

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Rituximab therapy for hairy cell leukemia: a retrospective study of 41 cases

et al. 2014

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“…Few preliminary data have reported that the combined use of rituximab after a purine nucleoside analogue, or given concomitantly with these agents, may produce a higher percentage of CR without evidence of residual disease and cumulative toxicity. [26][27][28] This chemotherapy-immunotherapy combination could increase the economic implications but, at the same time, in terms of cost/benefit balance, it is important to evaluate this aspect over a long period of time, because it could potentially be possible to reduce the number of further treatments for the patients.…”

Section: Discussionmentioning

confidence: 99%

Hairy cell leukemia

Zinzani

Pellegrini

Stefoni

et al. 2010

Cancer

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BACKGROUND: Historically, the first treatment choices for hairy cell leukemia (HCL) were splenectomy and alphainterferon. Recently, purine analogues (pentostatin and cladribine) changed radically the treatment modality, inducing complete and durable responses in the majority of patients. METHODS: The authors analyzed the outcome of different lines of therapy in 121 HCL patients followed in their institute from 1986 to 2008, with a median follow-up of 105 months. Patients were divided into subgroups according to the number of treatments; Group A included 121 patients who underwent a front-line therapy, Group B patients (n ¼ 53) were treated with 2 lines, Group C patients (n ¼ 34) with 3 lines, Group D patients (n ¼ 17) with 4 lines, and Group E patients (n ¼ 8) with 5 lines. RESULTS: In Group A, 92 (77%) patients obtained a complete response (CR), 23 (18%) a partial response, and the remaining 6 (5%) a minor or no response; median duration of response was 2.7 years. In Group B, 53 relapsed patients achieved a second CR rate of 73.5%; median duration of response was 2.5 years. Group C contained 34 patients in a second relapse, with a CR rate after the third line of treatment of 70.5% (median duration of response, 2.2 years). In Group D, 11 (64.7%) patients obtained a CR (median duration of response, 1.6 years), and in Group E 4 (50%) of 8 patients achieved a CR (median duration of response, 1.3 years). CONCLUSIONS: This study confirms the high risk (>40% of all patients) of retreatment of HCL patients and the need to maximize primary response. Cancer 2010;116:4788-92.

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“…As noted in the Scripps Clinic study, many asymptomatic patients with normal blood cell counts nearly 20 years after cladribine therapy still demonstrate MRD. 4 Cervetti et al 38 treated patients with rituximab sequentially after cladribine treatment but only administered the monoclonal antibody when MRD was detectable. With this protocol, rituximab was administered anytime from 1.5 to an astounding 113 months after cladribine (mean, 4.3 months).…”

Section: Sequential Therapymentioning

confidence: 99%

My Treatment Approach to Hairy Cell Leukemia

Naik

Saven

2012

Mayo Clinic Proceedings

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Hairy cell leukemia (HCL) is a rare chronic lymphoproliferative disorder characterized by circulating B cells with cytoplasmic projections, pancytopenia, splenomegaly, and a typical flow cytometry pattern. Recently, the BRAF V600E mutation was uniformly identified in one HCL series, which may provide insights into the pathogenic mechanisms. The disease course is usually indolent but inexorably progressive. Patients require treatment when they have significant cytopenia or occasionally recurrent infections from immunocompromise. In the mid-1980s, interferon replaced splenectomy as the initial treatment. A few years later, 2 purine nucleoside analogs, cladribine and pentostatin, showed promising activity in HCL. Complete response rates approached 95% with cladribine given as a single 7-day intravenous infusion. Newer methods of cladribine administration and modified dosing schedules have since been studied. Pentostatin response rates are comparable. We generally prefer cladribine because of its ease of administration, single infusion schema, and favorable toxicity profile. Since the introduction of these drugs, which have never been randomly compared, long-term follow-up studies have confirmed impressive and durable response durations. However, roughly 40% of patients with HCL eventually relapse. In this setting, patients can be re-treated with purine analogs. Rituximab also has a reasonable response rate in relapsed HCL; it can be given as a single agent sequentially after purine nucleosides or concurrently. Immunotoxins have robust responses but remain in development. Targeting the BRAF pathway will be an exciting future area of research. Many patients have minimal residual disease after initial treatment, but the clinical significance of this remains unknown. H airy cell leukemia (HCL) is a rare adult B-cell lymphoid leukemia characterized by pancytopenia, splenomegaly, and absolute monocytopenia. Morphologically, HCL is characterized by circumferential cytoplasmic projections (Figure 1). Bone marrow biopsy will reveal hypercellularity in most cases, with hairy cells having nuclei widely separated by abundant cytoplasm, giving a "fried-egg" appearance ( Figure 2). Classically, tartrate-resistant acid phosphatase activity confirmed the diagnosis of HCL.1 However, immunophenotyping by flow cytometry is now considered standard practice. Hairy cell leukemia is characterized by the B-cell antigens CD19, CD20, and CD22. In addition, they coexpress the surface antigens CD11c, CD25, and CD103. Hairy cells generally lack CD5, CD10, CD21, and CD23. Immunohistochemical stains for DBA44 and annexin A1 can also help confirm the diagnosis. PATHOGENESISFor decades, the cellular event leading to HCL has evaded scientists and clinical researchers. Recently, 47 patients with HCL in Italy had wholeexome gene sequencing performed on leukemic cells and matched nonleukemic cells. 2 In every patient, the well-known BRAF V600E mutation was identified. This mutation, more commonly known for its presence in melanoma, was a surpr...

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Rituximab as treatment for minimal residual disease in hairy cell leukaemia: extended follow‐up

Cited by 30 publications

References 10 publications

Rituximab therapy for hairy cell leukemia: a retrospective study of 41 cases

Rituximab therapy for hairy cell leukemia: a retrospective study of 41 cases

Hairy cell leukemia

My Treatment Approach to Hairy Cell Leukemia

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