High incidence of infections after 2-chlorodeoxyadenosine (2-CDA) therapy in patients with malignant lymphomas and chronic and acute leukaemias

Betticher, Daniel; Fey, Martin F.; Rohr, A. von; Tobler, Andreas; Jenzer, H R; Gratwohl, A; Lohri, Andreas; Pugin, P; Hess, U.; Pagani, Olivia; Zulian, Gilbert; Cerny, T.

doi:10.1093/oxfordjournals.annonc.a058693

Cited by 67 publications

(31 citation statements)

References 40 publications

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“…However, toxicity (myelotoxicity and infections, mainly of opportunistic type [12,[22][23][24]) and its rather complicated-way of administration are reasons to withhold the drug. We therefore aimed to simplify cladribine administration and to decrease the side effects by dose reduction.…”

Section: Discussionmentioning

confidence: 99%

Reduced dose of subcutaneous cladribine induces identical response rates but decreased toxicity in pretreated chronic lymphocytic leukaemia

Betticher¹,

Ratschiller²,

Schmitz³

et al. 1998

Annals of Oncology

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SummaryPurpose: To study the efficacy and the safety of cladribine (2-chlorodeoxyadenosine, 2-CDA) administered as 24-hour infusions or as subcutaneous bolus injections at two different doses to patients with relapsing or refractory chronic lymphocytic leukaemia (CLL).Patients and methods: In this non randomised 2-cohort study, 20 patients with pretreated CLL received cladribine at a dose of 0.7 mg/kg/cycle as continuous i.v. infusions over seven days (group 1) and 35 patients were treated at a reduced dose of 0.5 mg/kg/cycle given as s.c. bolus injections for five days (group 2). After two cycles of four week duration, response was assessed. In the case of progressive disease, therapy was discontinued, otherwise a maximum of four additional cycles were administered until best response.Results: A total of 130 cycles were administered (group 1: 41, group 2: 89). Patient characteristics in both groups were comparable. The median dose intensities were 0.172 mg/kg per week and 0.123 mg/kg per week for groups 1 and 2, respectively (P ^ 0.0001). The overall response rate for all 55 patients was 38% (95% confidence interval (95% CI): 25%-52%), with 5% CR and 33% PR. Response was similar in both patient groups (35% in group 1, 40% in group 2). No association between cladribine dose intensity and response rate was found, and there was no difference between patients relapsing after or refractory to previous therapies (11 of 24 vs. 10 of 31). Median remission duration was six months in both groups. Toxicity, in particular infections (all WHO grades, 34% in group 1 versus 7% in group 2) and myelosuppression (grade 1-4 neutropenia, 72% versus 41% of cladribine cycles) were statistically significantly more frequent in group 1.Conclusion: Cladribine is active in heavily pretreated patients with chronic lymphocytic leukaemias. Dose reduction by 29% led to similar response and remission duration, but to a significant decrease of myelotoxicity and risk of infection. Cladribine administered as s.c. bolus injections at 0.5 mg/kg per cycle is safe and this dose level should not be exceeded in this patient population.

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Section: Discussionmentioning

confidence: 99%

Reduced dose of subcutaneous cladribine induces identical response rates but decreased toxicity in pretreated chronic lymphocytic leukaemia

Betticher¹,

Ratschiller²,

Schmitz³

et al. 1998

Annals of Oncology

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“…In general, cladribine is well tolerated, but further hematological deterioration in the early stage of treatment as well as prolonged lymphopenia of the CD4 subset may occur following treatment and lead to infectious complications [61,62]. Cladribine is commonly chosen as the initial treatment.…”

Section: Treatmentmentioning

confidence: 99%

Hairy Cell Leukemia: An Elusive but Treatable Disease

Wanko

Castro

2006

The Oncologist

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Hairy cell leukemia (HCL) is a unique chronic lymphoproliferative disorder that can mimic or coexist with other clonal hematologic disorders and has been associated with autoimmune disorders. It should be entertained as an alternative diagnosis in patients with cytopenias being assigned the diagnosis of aplastic anemia, hypoplastic myelodysplastic syndrome, atypical chronic lymphocytic leukemia, B-prolymphocytic leukemia, or idiopathic myelofibrosis. Causative etiology or molecular defects remain unclear, although nonspecific chromosomal and molecular changes have been described. The typical presentation is that of a middle-aged man with an incidental finding of pancytopenia, splenomegaly, and inaspirable bone marrow. Treatment with a purine analogue, cladribine or pentostatin, results in extremely high, durable, overall, and complete response rates, although resistance and relapses do occur. A variant subtype exists and is frequently associated with a poor response. Because of its simplified dosing schedule, cladribine is commonly used as the initial therapy. Treatment of relapsed HCL is dictated by the duration of the preceding remission. Relapsed disease after a prolonged remission can often be successfully retreated with the same initial agent. Resistance in typical HCL is treated with the alternate purine analogue. New agents, such as rituximab and BL22, are actively being evaluated and show promising results in both HCL subtypes. This article uses two patients diagnosed with aplastic anemia and recently seen in consultation at our institution as a springboard to discuss the biology, pathogenesis, clinical presentation, diagnostic evaluation, and treatment options of HCL. The Oncologist 2006;11:780-789

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“…[12][13][14]20 Increased risks of repetitive administration of nucleoside analogs include: persistent CD4 lymphocytopenia, marrow aplasia and prolonged cytopenias requiring transfusion support, neutropenic febrile episodes and infections, and neurotoxicity that may be life-threatening. 15,[21][22][23][24] Alternative salvage strategies were sought at our institution after 2 patients with long initial CRs (5 and 7 years, respectively) developed prolonged myelosuppression after retreatment with 2-CdA for relapsed HCL and succumbed to fatal systemic fungal infections.…”

Section: Introductionmentioning

confidence: 99%

Rituximab in relapsed or refractory hairy cell leukemia

Thomas

O’Brien

Bueso‐Ramos

et al. 2003

Blood

155

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The purpose of this study was to investigate the efficacy and safety of the monoclonal antibody, rituximab, in relapsed or refractory hairy cell leukemia (HCL). Fifteen patients with relapsed or primary refractory HCL after nucleoside analogs received rituximab 375 mg/m 2 weekly for a total of 8 planned doses. An additional 4 doses could be administered to responders who had not achieved complete response (CR). The overall response rate was 80%. Eight patients (53%) achieved CR, 2 (13%) attained CR by hematologic parameters with residual marrow disease (1% to 5% marrow hairy cells), and 2 (13%) had a partial response. Of the 12 responders followed for a median of 32 months (range, 8 to 45؉ months), 5 patients (

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High incidence of infections after 2-chlorodeoxyadenosine (2-CDA) therapy in patients with malignant lymphomas and chronic and acute leukaemias

Cited by 67 publications

References 40 publications

Reduced dose of subcutaneous cladribine induces identical response rates but decreased toxicity in pretreated chronic lymphocytic leukaemia

Reduced dose of subcutaneous cladribine induces identical response rates but decreased toxicity in pretreated chronic lymphocytic leukaemia

Hairy Cell Leukemia: An Elusive but Treatable Disease

Rituximab in relapsed or refractory hairy cell leukemia

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