The efficacy of methotrexate for lymphomatoid papulosis
2015; Elsevier BV; Volume: 72; Issue: 6 Linguagem: Inglês
10.1016/j.jaad.2015.03.001
ISSN1097-6787
AutoresKate Newland, Christopher McCormack, Robert Twigger, Odette Buelens, Charlotte FM Hughes, Stephen Lade, Michael Dickinson, Lee Mei Yap, Gail Ryan, H. Miles Prince,
Tópico(s)Fungal Infections and Studies
ResumoTo the Editor: Lymphomatoid papulosis (LyP) is a CD30+ lymphoproliferative disorder, a group that includes primary cutaneous anaplastic large cell lymphoma and "borderline cases."1Willemze R. Jaffe E.S. Burg G. et al.WHO-EORTC classification for cutaneous lymphomas.Blood. 2005; 105: 3768-3785Crossref PubMed Scopus (3259) Google Scholar Low-dose methotrexate (5 to 25 mg weekly) is the most commonly reported single agent chemotherapy used to treat LyP,2Kempf W. Pfaltz K. Vermeer M.H. et al.EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma.Blood. 2011; 118: 4024-4035Crossref PubMed Scopus (325) Google Scholar with retrospective studies finding that it effectively suppresses the development of new lesions.2Kempf W. Pfaltz K. Vermeer M.H. et al.EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma.Blood. 2011; 118: 4024-4035Crossref PubMed Scopus (325) Google Scholar, 3Bekkenk M.W. Geelan F.A. van Voorst Vader P.C. et al.Primary and secondary cutaneous CD30+ lymphoproliferative disorders: a report from the Dutch Cutaneous Lymphoma Group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment.Blood. 2000; 95: 3653-3661PubMed Google Scholar, 4Kadin M.E. Current management of primary cutaneous CD30+ lymphoproliferative disorders.Oncology (Williston Park). 2009; 23: 1158-1164PubMed Google Scholar, 5Vonderheid E.C. Sajjadian A. Kadin M.E. Methotrexate is effective therapy for lymphomatoid papulosis and other primary cutaneous CD30-positive lymphoproliferative disorders.J Am Acad Dermatol. 1996; 34: 470-481Abstract Full Text PDF PubMed Scopus (157) Google Scholar European Organization for Research and Treatment of Cancer (EORTC), the International Society for Cutaneous Lymphomas (ISCL), and the United States Cutaneous Lymphoma Consortium (USCLC) guidelines describe a rapid relapse rate of 63% following methotrexate cessation, indicating that long-term maintenance therapy is often required.2Kempf W. Pfaltz K. Vermeer M.H. et al.EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma.Blood. 2011; 118: 4024-4035Crossref PubMed Scopus (325) Google Scholar, 3Bekkenk M.W. Geelan F.A. van Voorst Vader P.C. et al.Primary and secondary cutaneous CD30+ lymphoproliferative disorders: a report from the Dutch Cutaneous Lymphoma Group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment.Blood. 2000; 95: 3653-3661PubMed Google Scholar, 4Kadin M.E. Current management of primary cutaneous CD30+ lymphoproliferative disorders.Oncology (Williston Park). 2009; 23: 1158-1164PubMed Google Scholar, 5Vonderheid E.C. Sajjadian A. Kadin M.E. Methotrexate is effective therapy for lymphomatoid papulosis and other primary cutaneous CD30-positive lymphoproliferative disorders.J Am Acad Dermatol. 1996; 34: 470-481Abstract Full Text PDF PubMed Scopus (157) Google Scholar No data are available regarding factors that may predispose patients to methotrexate dependence. Our study evaluated the safety and efficacy of methotrexate in our patient cohort. We also sought to identify factors that may predict which patients are more likely to require long-term maintenance therapy. Retrospective analysis of the cutaneous lymphoma database at Peter MacCallum Cancer Centre and St Vincent's Hospital, Melbourne, Australia, representing a 39-year period, was undertaken. Data collection and analysis was approved in accordance with the Human Research Ethics Committee at our institution. Fifty-three patients fulfilled the WHO-EORTC classification of LyP based on clinical and histopathologic criteria.1Willemze R. Jaffe E.S. Burg G. et al.WHO-EORTC classification for cutaneous lymphomas.Blood. 2005; 105: 3768-3785Crossref PubMed Scopus (3259) Google Scholar Patients were treated per physician's choice. Patient demographic and disease characteristics are outlined in Table I.Table IPatient and disease characteristics of study populationAll, no. (%)Observation cohort No (% of cohort)Methotrexate dependent No (% of cohort)Methotrexate successfully weaned No (% of cohort)P valueAll53 (100)20 (38)16 (30)6 (11)Gender1.0 Female24 (45)10 (50)9 (56)3 (50) Male29 (55)10 (50)7 (44)3 (50)Age at diagnosis (median + range)39 (3-77)40 (3-77)50 (8-77)30.5 (21-66).4375 Female34 (8-77)43 (27-77)54 (8-76)30 (21-31) Male39 (3-77)27 (3-63)52 (19-77)47 (26-66)LyP Subtype.8054 A40 (75)14 (70)13 (81)5 (83) B4 (8)1 (5)1 (6)0 (0) C8 (15)4 (20)2 (13)1 (17) D1 (2)1 (5)0 (0)0 (0)T stage at diagnosis.1602 T114 (26)12 (60)1 (6)1 (17) T27 (13)1 (5)1 (6)2 (33) T332 (60)7 (35)14 (88)3 (50)Associated lymphomaN/A MF10 (19)3 (15)4 (25)0 (0) PC-ALCL10 (19)2 (10)3 (19)2 (33)Hematologic/solid organ malignancy4 (8)0 (0)2 (13)2 (33)N/AData analysis of methotrexate dependent and methotrexate successfully weaned groups. Analysis was performed in GraphPad Prism 6.0 (GraphPad Software, San Diego, CA). Categorical variables were analyzed using Fisher's exact test or chi-square test. Continuous variable were compared using the nonparametric Mann-Whitney test. A P-value of less than .05 was considered significant.LyP, Lymphomatoid papulosis; T, tumor; MF, mycosis fungoides; PC-ALCL, primary cutaneous anaplastic large cell lymphoma.LyP subtypes (EORTC-WHO definition):Type A lesions, scattered or small clusters of large, sometimes multinucleated or Reed-Sternberg-like, CD30+ cells, intermingled with numerous inflammatory cells.Type B lesions, epidermotropic infiltrate of small atypical cells with cerebriform nuclei.Type C lesions, monotonous population or large clusters of large CD30+ T cells with relatively few admixed inflammatory cells.Type D lesions, epidermotropism of CD8+ cytotoxic T lymphocytes demonstrating CD30 positivity.T stages (ISCL/EORTC TNM Classification of Cutaneous Lymphomas other than MF/SS):T1, solitary skin involvement.T2, regional skin involvement (multiple lesions limited to one body region or two contiguous body regions).T3, generalized skin involvement. Open table in a new tab Data analysis of methotrexate dependent and methotrexate successfully weaned groups. Analysis was performed in GraphPad Prism 6.0 (GraphPad Software, San Diego, CA). Categorical variables were analyzed using Fisher's exact test or chi-square test. Continuous variable were compared using the nonparametric Mann-Whitney test. A P-value of less than .05 was considered significant. LyP, Lymphomatoid papulosis; T, tumor; MF, mycosis fungoides; PC-ALCL, primary cutaneous anaplastic large cell lymphoma. LyP subtypes (EORTC-WHO definition):Type A lesions, scattered or small clusters of large, sometimes multinucleated or Reed-Sternberg-like, CD30+ cells, intermingled with numerous inflammatory cells.Type B lesions, epidermotropic infiltrate of small atypical cells with cerebriform nuclei.Type C lesions, monotonous population or large clusters of large CD30+ T cells with relatively few admixed inflammatory cells.Type D lesions, epidermotropism of CD8+ cytotoxic T lymphocytes demonstrating CD30 positivity. T stages (ISCL/EORTC TNM Classification of Cutaneous Lymphomas other than MF/SS):T1, solitary skin involvement.T2, regional skin involvement (multiple lesions limited to one body region or two contiguous body regions).T3, generalized skin involvement. Those deemed to require methotrexate were dosed as per our policy of 20 to 30 mg/wk orally for a minimum of 6 months (if responding), followed by a 2- to 6-month weaning period. We defined methotrexate dependence as (1) an inability to wean methotrexate below 5 mg weekly without progressive disease (PD) or relapse and/or (2) relapse or PD less than or equal to 6 months after drug cessation. The term methotrexate successfully weaned was defined as (1) cessation of methotrexate therapy with a partial or complete response (PR or CR) to treatment and (2) maintenance of this response for greater than or equal to 6 months. A group labeled observation cohort received no treatment for LyP apart from intermittent topical corticosteroid application. Not surprisingly, given that therapeutic intervention was based on physician judgment, our observation cohort had milder disease (Table I). Methotrexate was the most common treatment for LyP, with 47% (n = 25) of patients receiving the drug at some point. We measured best response to treatment with methotrexate; 44% (n = 11) patients had CR, 44% (n = 11) had PR, and 12% (n = 3) had PD. Of patients treated with methotrexate, 64% (n = 16) remained methotrexate-dependent, 24% (n = 6) were successfully weaned off drug, and 12% (n = 3) ceased treatment due to PD (Fig 1). The patient and disease characteristics of the methotrexate-dependent and the methotrexate successfully weaned groups were compared to determine any factors predicting which patients were more likely to be successfully weaned off drug (Table I). None were identified, although a numerical trend suggested that younger patients may be easier to wean off methotrexate (median age 30.5 vs 50 years). Methotrexate was extremely well tolerated by our cohort. The only reported significant adverse drug reactions were single episodes of chronic thrombocytopenia and severe nausea. Our study demonstrates that once systemic therapy is deemed necessary, methotrexate is effective with limited toxicity, but two-thirds of patients remain methotrexate-dependent and it is not possible to predict which patients will successfully wean off drug. CorrectionJournal of the American Academy of DermatologyVol. 73Issue 3PreviewNewland KM, McCormack CJ, Twigger R, et al. The efficacy of methotrexate for lymphomatoid papulosis. J Am Acad Dermatol. 2015;72:1088-1090. Full-Text PDF
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