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Carboplatin instead of cisplatin in combination with dexamethasone, high-dose cytarabine with or without rituximab (DHAC+/−R) is an effective treatment with low toxicity in Hodgkin’s and non-Hodgkin’s lymphomas

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Abstract

The DHAP regimen (high-dose cytarabine in combination with dexamethasone and cisplatin) with or without rituximab (DHAP+/−R) is one of the most common regimens in daily practice. It is considered the standard treatment for relapse or refractory Hodgkin’s and non-Hodgkin’s lymphoma (NHL). Cisplatin nephrotoxicity is a major concern, and other platinum compounds are being tried. We performed a monocentric retrospective analysis to evaluate the use of carboplatin, so-called DHAC+/−R regimen. The purpose was to assess the toxicity of the DHAC+/−R regimen in real-life. The Dexamethasone, Cytarabine, Carboplatin (DHAC) regimen consisted of carboplatin AUC = 5 mg/ml/min (targeted area under the curve with Calvert’s formula) on day 1, cytarabine 2 g/m2 twice a day on day 2 and IV dexamethasone 40 mg from days 1 to 4. Rituximab was administrated at 375 mg/m2 on day 1 for CD20+ NHL. The interval between courses was 21 days. During the period considered, 199 patients received DHAC+/−R. For the entire cohort, median follow-up is 24 months (range, 2–82), median OS is not reached (NR), estimated 2-year OS is 75% (95% CI, 69–83) and median progression-free survival (PFS) is 46 months (95% CI, 22-NA). Of 144 patients scheduled for autologous stem cell transplantation (ASCT), 102 (71%, NA = 2) were in response after DHAC+/−R and all except 4 underwent ASCT. Grade ≥ 3 haematological toxicities were mainly thrombocytopenia (n = 101) and anaemia (n = 95). Grade ≥ 3 neutropenia occurred in 10 patients. No grade ≥ 3 renal and one grade 3 neurological toxicity were reported. DHAC+/−R is feasible in daily practice, provides good response rates and jeopardises neither stem cell collection nor ASCT.

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Acknowledgements

The authors acknowledge the support of the nurses of the Haematology Department of Nantes Medical University (France), the patients and their families. The data was collected from our database (Lhenabase).

BT is the recipient for a fellowship from Fondation ARC pour la Recherche contre le Cancer.

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Author notes

  1. B. Tessoulin and P. Thomare have contributed equally to this work

Authors and Affiliations

  1. Service d’hématologie clinique, CHU de Nantes, place Alexis Ricordeau, 44000, Nantes, France

    B. Tessoulin, T. Gastinne, B. Mahé, N. Blin, V. Dubruille, C. Touzeau, J. S. Boudreault, F. Perrin, A. Lok, T. Guillaume, A. Garnier, P. Peterlin, P. Gallas, P. Chevallier, P. Moreau & Steven Le Gouill

  2. INSERM, UMR892, Equipe 10, Nantes, France

    B. Tessoulin & Steven Le Gouill

  3. Pharmacy Clinical Oncology Unit (UPCO), Department of Pharmacy, University Hospital of Nantes, Nantes, France

    P. Thomare, E. Delande & J. Moynard

  4. Department of Pathology, University Hospital of Nantes, Nantes, France

    A. Moreau & C. Bossard

  5. INSERM, CIC 004, Nantes University Hospital, Nantes, France

    Steven Le Gouill

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  1. B. Tessoulin
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  2. P. Thomare
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Corresponding author

Correspondence to Steven Le Gouill.

Ethics declarations

According to French legislation (articles L. 1121-1 paragraph 1 and R1121-2, Public Health Code), this observational retrospective study using non-transplanted patient data requires neither informed consent nor ethics committee approval. All transplanted patients signed an informed consent and were reported to the EBMT Registry Database.

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Table 1

Dosings (g/m2). Carbo x: Carboplatin infusion at time xth, Cyta x: Cytarabine infusion at time xth, <70y: patients less than 70 years old, >=70y: patients 70years-old or older. (DOCX 18 kb)

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Tessoulin, B., Thomare, P., Delande, E. et al. Carboplatin instead of cisplatin in combination with dexamethasone, high-dose cytarabine with or without rituximab (DHAC+/−R) is an effective treatment with low toxicity in Hodgkin’s and non-Hodgkin’s lymphomas. Ann Hematol 96, 943–950 (2017). https://doi.org/10.1007/s00277-017-2981-2

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  • DOI: https://doi.org/10.1007/s00277-017-2981-2

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