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Biweekly cladribine and rituximab in a patient with hairy cell leukemia and severe renal failure

Ena Ranković

Division of Hematology, Department of Internal medicine, University Hospital Centre Zagreb, Croatia

E-mail : bhuvaneswari.bibleraaj@uhsm.nhs.uk

Snježana Dotlić

Department of Pathology, University Hospital Centre Zagreb, Croatia

Medical School, University of Zagreb, Croatia

Pavle Rončević

Division of Hematology, Department of Internal medicine, University Hospital Centre Zagreb, Croatia

Marijo Vodanović

Division of Hematology, Department of Internal medicine, University Hospital Centre Zagreb, Croatia

Igor Aurer

Division of Hematology, Department of Internal medicine, University Hospital Centre Zagreb, Croatia

Medical School, University of Zagreb, Croatia

DOI: 10.15761/CCRR.1000485

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Abstract

Hairy cell leukemia (HCL) is a rare indolent lymphoproliferative disorder usually clinically characterized by pancytopenia and splenomegaly. It is very sensitive to purine analogues cladribine and pentostatin which are both primarily excreted by kidneys and registration labels bear warnings against their use in patients with severe renal insufficiency. We report a patient with HCL and severe renal failure who was successfully treated with five subcutaneous injections of cladribine 0.14 mg/kg and six biweekly infusions of rituximab 375 mg/2 iv. This regimen was tolerated remarkably well without cumbersome side–effects. Our case-report suggests that cladribine can be efficaciously and safely used in patients with severe renal insufficiency if administered in standard doses once every two weeks.

Key words

hairy cell, leukemia, renal insufficiency, cladribine, rituximab

Case presentation

Hairy cell leukaemia (HCL) is a rare indolent lymphoproliferative disorder usually clinically characterized by pancytopenia and splenomegaly [1]. Small mature lymphoid cells with hairy cytoplasmic projections expressing B-cell markers, CD22, CD11c, CD103, CD25, CD123, DBA44, FMC-7 and negative for CD10 and CD5 are found in the bone marrow and spleen. Most cases harbor B-raf mutations. HCL is extremely sensitive to purine analogues cladribine and pentostatin [2-4]. After a single treatment cycle more than 90% of patients obtain remissions lasting more than 5 years. Overall, 10-year survival exceeds 90%. Both drugs are primarily excreted by kidneys [5,6] and registration labels bear warnings against their use in patients with severe renal insufficiency [7,8]. The European Medical Agency label for cladribine mentions severe renal insufficiency as a contraindication for its use, therefore treatment of HCL patients with kidney failure remains a challenge. Here we report such a patient successfully treated with the combination of cladribine and rituximab.

A 75-year old man was admitted to our hospital for evaluation of severe kidney failure and preparation for chronic dialysis. His creatinine clearance was 10 ml/min and proteinuria 0.35 g/day. He had pancytopenia (WBC 2.67 × 109/L with 53% lymphocytes, RBC 2.64 × 1012/L, Hgb 82 g/L, platelets 59 × 109/L) without hepatosplenomegaly or lymphadenopathy. Kidneys were small, consistent with chronic renal disease. A trephine biopsy was performed and HCL diagnosed. The patient was treated with five subcutaneous injections of cladribine 0.14 mg/kg and six biweekly infusions of rituximab 375 mg/2 iv. Toxicity was acceptable; granulocytopenia and thrombocytopenia were brief and mild; RBC transfusions were given twice. Neither infections nor other non-haematological toxicities occurred. A repeated trephine biopsy showed complete clearance of tumour cells. At follow-up 8 years after treatment the patient is still in complete remission, on chronic dialysis. Interestingly, he was treated for 2 non-melanoma skin cancers a few years after HCL treatment with cladribine.

Purine analogues used in HCL are excreted through kidneys, 80% of the total administered dose of pentostatine and around 30% of cladribine are found in the urine [5,6]. In patients with renal failure, the area under the curve of cladribine is larger than in patients with normal kidney function resulting in more prolonged pancytopenia. Data suggest that weekly administration of cladribine is similarly effective as daily administration [9]. We speculated that more widely spaced dosing would reduce the risk of drug accumulation, enable us to follow haematological toxicity more closely and if necessary, stop the treatment before the total planned amount of cladribine was administered. Any reduction in antitumor effect of cladribine could be countered by rituximab which is not excreted by kidneys, but less active as monotherapy than purine analogues [10]. The treatment was tolerated remarkably well without cumbersome side–effects. This case-report suggests that cladribine can be efficaciously and safely used in patients with severe renal insufficiency if administered in standard doses once every two weeks.

Funding

Supported in part by grant 108-1081872-1908 from the Croatian Ministry of Science.

Conflicts of interest

IA and SD have received honoraria and/or research support from Roche and/or its affiliates.

References

  1. Foucar K, Falini B, Stein H (2017) Hairy cell leukaemia. In: WHO classification of tumours of haematopoietic and lymphoid tissues. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA (eds). IARC Lyon, pp: 226-228.
  2. Dearden CE, Else M, Catovsky D (2011) Long-term results for pentostatin and cladribine treatment of hairy cell leukemia. Leuk Lymphoma 2: 21-24. [Crossref]
  3. Aurer I, Mitrovic Z, Kovacevic-Metelko J, Radman I, Basic-Kinda S, et al. (2007) Treatment of hairy cell leukemia with cladribine. Lijec Vjesn 129: 80-83.
  4. Thompson PA, Ravandi F (2017) How I manage patients with hairy cell leukaemia. Br J Haematol 177: 543-556. [Crossref]
  5. Malspeis L, Weinrib AB, Staubus AE, Grever MR, Balcerczak SP, et al. (1984) Clinical pharmacokinetics of 2’-deoxycoformycin. Cancer Treat Symp 2: 7-15.
  6. Liliemark J (1997) The clinical pharmacokinetics of cladribine. Clin Pharmacokinetics 32:120-131.
  7. https://www.ema.europa.eu/en/medicines/human/EPAR/mavenclad
  8. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022561s000lbl.pdf
  9. Zenhausern R, Hsu Schmitz SF, Solenthaler M, Heim D, Meyer-Monard S, et al. (2009) Randomized trial of daily versus weekly administration of 2-chlorodeoxyadenosine in patients with hairy cell leukemia: A multicenter phase III trial (SAKK 32/98). Leuk Lymphoma 50: 1501-1511. [Crossref]
  10. Hagberg H, Lundholm L (2001) Rituximab, A chimaeric anti-CD20 monoclonal antibody, in the treatment of hairy cell leukaemia. Br J Haematol 115: 609-611. [Crossref]

Editorial Information

Editor-in-Chief

Andy Goren
University of Rome, Italy

Article Type

Case Report

Publication history

Received date: July 17, 2020
Accepted date: July 22, 2020
Published date: July 29, 2020

Copyright

©2020 Ranković E, Snježana D and Rončević P. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

©2020 Ranković E. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Clin Case Rep Rev, 6: DOI: 10.15761/CCRR.1000485

Corresponding author

Ena Ranković

Division of Hematology, Department of Internal Medicine, University Hospital Centre Zagreb, Kispaticeva 12, HR-1000 Zagreb, Croatia

E-mail : bhuvaneswari.bibleraaj@uhsm.nhs.uk

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