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Folinic acid administration following MTX as prophylaxis for GVHD

Bone Marrow Transplantation volume 44, page 257 (2009)Cite this article

Bhurani et al. recently summarized in your columns1 the Australian and New Zealand approaches to giving or not giving folinic acid following MTX for GVHD prophylaxis in allogeneic hematopoietic SCT (HSCT). They showed in their comprehensive and interesting paper that its use varied very greatly. They noted as well the absence of background information at the user's institution on why to administer folinic acid. The authors referred to some reports on the use of combined MTX with folinic acid in patients with rheumatoid arthritis and autoimmune conditions. They also mentioned the use of folinic acid in patients given MTX on high- and intermediate-dose chemotherapy protocols.

There are indeed data that provide a rationale for using MTX and folinic acid in combination for GVHD prophylaxis. Leucovorin (folinic acid) was clearly shown in a prospective randomized comparative study in dogs with DLA (dog leukocyte Ag)-mismatched allogeneic BM transplants to reduce toxicity when it was given 6 h after each dose of MTX, and the effect on prevention of GVHD was maintained.2 These clinical transplant studies were based on clear in vitro and in vivo findings. When dogs were given either sheep RBCs or allogeneic blood cells, repeated doses of MTX followed by leucovorin 6 h after each dose completely abrogated the development of antibodies without any signs of toxicity in the animals. All control animals given MTX alone died of toxicity. In vitro studies showed that MTX at concentrations above 10−6 M completely abrogated thymidine uptake in lymphocytes on stimulation for 6 h.3

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References

  1. Bhurani D, Schifter M, Kerridge I . Folinic acid administration following MTX as prophylaxis for GVHD in allogeneic HSCT centres in Australia and New Zealand. Bone Marrow Transplant 2008; 42: 547–550.

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  2. Gratwohl AA, Bull MI, Graw Jr RG, Norton L, Knutsen T . Methotrexate and citrovorum factor after histoincompatible allogeneic bone marrow transplants in dogs. Acta Haematol 1978; 60: 233–242.

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  3. Gratwohl A, Deisseroth A . Suppression of humoral immune response with methotrexate and citroforum factor. In: International Society of Chemotherapy (eds). Current Chemotherapy. American Society for Microbiology, 1978, pp 1262–1263.

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  1. Department of Hematology, University Hospital, University of Basel, Basel, Switzerland

    A Gratwohl

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  1. A Gratwohl
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Gratwohl, A. Folinic acid administration following MTX as prophylaxis for GVHD. Bone Marrow Transplant 44, 257 (2009). https://doi.org/10.1038/bmt.2009.4

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