Progressive multifocal leukoencephalopathy in a patient with systemic mastocytosis treated with cladribine

Alstadhaug, Karl Bjørnar; Halstensen, Randi Fykse; Odeh, Francis

doi:10.1016/j.jcv.2016.12.005

Cited by 20 publications

(18 citation statements)

References 15 publications

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“…One patient required allogeneic [4]. A fatal case of progressive multifocal leukoencephalopathy (PML) after 2-CdA for mastocytosis as a consequence of prolonged lymphopenia has been recently published [2]. Overall response rates were comparable between our study and those presented by others [4,10,11].…”

Section: Discussionsupporting

confidence: 76%

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The Efficacy of Cladribine (2-CdA) in Advanced Systemic Mastocytosis

Helbig

Koclęga

Gawel³

et al. 2020

Indian J Hematol Blood Transfus

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Systemic mastocytosis (SM) is a rare clonal disorder with multi-organ involvements and shortened life expectancy. To date, no curative treatment for SM exists. Cladribine (2-CdA) is a purine analogue showing activity against neoplastic mast cells and its use was found to be effective in some patients with SM. Nine patients (six males and three females) with advanced SM at median age of 63 years (range 33-67) who received at least one course of 2-CdA were included in a retrospective analysis. Study patients were classified as having aggressive SM (ASM; n = 7) and SM with an associated hematological neoplasm (SM-AHN; n = 2). The ''C'' findings were as follows: (1) absolute neutrophil count (ANC) \ 1 9 10 9 /l (n = 1) and/ or hemoglobin level\ 10 g/dl (n = 4) and/or platelet count \ 100 9 10 9 /l (n = 4); (2) hepatomegaly with ascites (n = 4); (3) skeletal involvement (n = 2); (4) palpable splenomegaly with hypersplenism (n = 3) and (5) malabsorption with weight loss (n = 5). Treatment consisted of 2-CdA at dose 0.14 mg/kg/day intravenously over a 2-h infusion for 5 consecutive days. Median dose per cycle was 45 mg (range 35-60). Median number of cycles was 6 (range 1-7). Overall response rate (ORR) was 66% (6/9 pts) including three partial responses and three clinical improvements. ORR was 100% and 66% for SM-AHN and ASM, respectively. Median duration of response was 1.98 years (range 0.2-11.2). At the last contact, five patients died, four have little disease activity, but remain treatment-free. 2-CdA seems to be beneficial in some patients with SM, however the response is incomplete.Keywords Aggressive systemic mastocytosis Á Cladribine Á Systemic mastocytosis with an associated hematological neoplasm Á KITD816V Á Response

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Section: Discussionsupporting

confidence: 76%

“…Two solid tumors were observed after long-term follow-up [ 4 ]. A fatal case of progressive multifocal leukoencephalopathy (PML) after 2-CdA for mastocytosis as a consequence of prolonged lymphopenia has been recently published [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of Cladribine (2-CdA) in Advanced Systemic Mastocytosis

Helbig

Koclęga

Gawel³

et al. 2020

Indian J Hematol Blood Transfus

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“…Several PML cases have been described in lymphoma patients receiving polychemotherapy including alemtuzumab, but lymphoma is a PML risk factor itself as well 57. A few PML cases have been described in patients treated intravenously with cladribine,72 but there have been no cases of PML with oral cladribine.…”

Section: Epidemiology Of Pmlmentioning

confidence: 99%

<p>Progressive Multifocal Leukoencephalopathy: Current Insights</p>

Kartau¹,

Sipilä²,

Auvinen³

et al. 2019

DNND

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Cases of PML should be evaluated according to predisposing factors, as these subgroups differ by incidence rate, clinical course, and prognosis. The three most significant groups at risk of PML are patients with hematological malignancies mostly previously treated with immunotherapies but also untreated, patients with HIV infection, and patients using monoclonal antibody (mAb) treatments. Epidemiological data is scarce and partly conflicting, but the distribution of the subgroups appears to have changed. While there is no specific anti-JCPyV treatment, restoration of the immune function is the most effective approach to PML treatment. Research is warranted to determine whether immune checkpoint inhibitors could benefit certain PML subgroups. There are no systematic national or international records of PML diagnoses or a risk stratification algorithm, except for MS patients receiving natalizumab (NTZ). These are needed to improve PML risk assessment and to tailor better prevention strategies.

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“…PML has not been reported in MS patients treated with cladribine, but has been observed in patients treated with cladribine for malignant diseases. 72…”

Section: Cladribinementioning

confidence: 99%

Pulsed immune reconstitution therapy in multiple sclerosis

Sørensen

Sellebjerg

2019

Ther Adv Neurol Disord

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Whereas drugs used for maintenance/escalation therapy do not maintain their beneficial effect after cessation of therapy, some new highly effective therapies can show prolonged treatment effects after a short treatment course. Such therapies have been named pulsed immune reconstitution therapies or pulsed immunosuppressive therapies, and typical representatives are alemtuzumab and cladribine. Autologous haematopoietic stem cell transplantation could be considered as the strongest immune reconstitution therapy. Both alemtuzumab and cladribine induce depletion of lymphocytes, and a common mechanism of action is preferential depletion of class-switched and unswitched memory B-cells. Whereas CD-19+ B-lymphocytes repopulate within 6 months, CD4+ T-cells repopulate at a slower rate, taking 1–2 years to reach the lower level of normal. In general, the depletion of lymphocytes is more profound and the repletion of T-cells is slower after alemtuzumab than after cladribine treatment. Both drugs have a strong effect on relapses and magnetic resonance imaging (MRI) activity, and reduce disability worsening. The therapeutic effect is maintained beyond the period of active treatment in a large proportion of patients, which is best documented for alemtuzumab. Adverse effects include reactivation of latent infections such as tuberculosis and risk of herpes zoster. The main disadvantage in alemtuzumab-treated patients is the risk of secondary immune-mediated disorders. Pulsed immune reconstitution therapy is an option as initial therapy in relapsing-remitting multiple sclerosis patients with high disease activity and in patients on treatment with another disease-modifying therapy with significant relapse and/or MRI activity.

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Progressive multifocal leukoencephalopathy in a patient with systemic mastocytosis treated with cladribine

Cited by 20 publications

References 15 publications

The Efficacy of Cladribine (2-CdA) in Advanced Systemic Mastocytosis

The Efficacy of Cladribine (2-CdA) in Advanced Systemic Mastocytosis

<p>Progressive Multifocal Leukoencephalopathy: Current Insights</p>

Pulsed immune reconstitution therapy in multiple sclerosis

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