A Single-Centre Experience of Methotrexate in the Management of Pure Red Cell Aplasia and Pure White Cell Aplasia

Pure red cell aplasia (PRCA) is a rare disorder characterised by severe anaemia with a reduction or absence of red cell precursors in the bone marrow. There are few case series reporting the use of low dose weekly oral methotrexate in PRCA. We describe 5 patients in whom methotrexate was used in the management of PRCA. We also report one case of a patient with pure white cell aplasia managed with methotrexate.

Patients were identified via a search of our bone marrow failure registry with the terms ‘pure red cell aplasia’, ‘pure white cell aplasia’ and ‘methotrexate’. Their electronic patient records were reviewed and information on treatment, response and side effects obtained.

Five patients with PRCA were identified, ranging in age from 39-93 years old (median age 80 years). The mean hemoglobin at diagnosis was 64g/L (range 47-84g/L). Four out of five patients had received other lines of treatment prior to methotrexate; these included cyclosporine, corticosteroids, tacrolimus, rituximab, alemtuzumab and cyclophosphamide. The mean number of treatments prior to methotrexate was 2 (range 0 to 6), with cyclosporine noted to be the most frequent previous treatment in 3 patients. The median starting dose of methotrexate was 10mg weekly (range 2.5mg - 10mg), with a median maximum dose reached of 10mg (range 5mg - 25mg). Four patients achieved a response with normalisation of hemoglobin in two patients, transfusion independence in one patient and reduction in transfusion requirements by approximately 50% in another. Mean time to response was 3.5 months (range: 1 week - 8 months). A 93-year-old female did not respond; however, dose escalation was limited due to progressive thrombocytopenia and nausea with a maximum tolerated dose of 5mg. The patient's platelet count fell from 111x10⁹/L to 45 x10⁹/L. Methotrexate was well tolerated overall, with transaminitis and thrombocytopenia limiting dose escalation in 1 and 3 patients respectively. We also report the case of a 61-year-old patient diagnosed with pure white cell aplasia secondary to a thymoma with Good's syndrome. Initial management included resection of the thymoma and granulocyte-colony stimulating factor injections, and subsequently cyclosporine. Methotrexate was then commenced alongside cyclosporine due to progressive neutropenia, with a gradual dose escalation to 10mg weekly. Hematological response with a neutrophil count of 6.29x10⁹/L was seen within 3 weeks, and her neutrophil count has remained consistently above 1x10⁹/L since commencing methotrexate 12 months ago.

We have seen good response rates to methotrexate in both PRCA and in a patient with pure white cell aplasia, with 5 out of 6 patients showing at least a partial response to treatment, giving an overall response rate of 83.3%. Methotrexate is generally well tolerated. Weekly oral low dose methotrexate appears to be an effective treatment for PRCA and pure white cell aplasia and should be considered as a management option for patients, especially those who have not responded or are intolerant to initial lines of treatment.

Kelly:F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: All authors received support for third-party writing assistance, furnished by Scott Battle, PhD, CMPP, of Nucleus Global, an Inizio company, and funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland.; Otsuka: Consultancy, Honoraria, Speakers Bureau; Biologix: Speakers Bureau; Sobi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees; Astellas: Speakers Bureau; Florio: Consultancy, Honoraria, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Munir:Janssen, AbbVie, AstraZeneca, Alexion, Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees. Muus:Roche: Membership on an entity's Board of Directors or advisory committees; Novartis UK: Membership on an entity's Board of Directors or advisory committees; Novartis Global: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Sobi Middle East: Speakers Bureau. Griffin:Omeros: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Regeneron Pharmaceuticals: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biocryst: Consultancy; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sobi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.