Clinical management for other iatrogenic immunodeficiency-associated lymphoproliferative disorders

Abstract

Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD), a category of immunodeficiency-associated LPD according to the World Health Organization classification, is associated with immunosuppressive drugs (ISDs). Several factors, including autoimmune disease (AID) activity, Epstein-Barr virus (EBV) infection, ISD usage, and aging, influence the development of OIIA-LPD, resulting in complicated clinical courses and outcomes. Most OIIA-LPD develops in patients with rheumatoid arthritis using methotrexate (MTX-LPD). The management of MTX-LPD is based on the clinical course, i.e., with/without regression, with/without relapse/regrowth event (RRE), LPD subtype, and ISDs for AIDs after LPD development. There are three clinical courses after ISD withdrawal: regressive LPD without relapse/regrowth (R-G), regressive LPD with RRE (R/R-G), and persistent LPD (P-G). The majority of EBV+ diffuse large B-cell lymphomas are classified in R-G, whereas classic Hodgkin lymphoma is generally classified in R/R-G. Polymorphic LPD (P-LPD) in MTX-LPD develops with heterogeneous pathological features similar to monomorphic LPD. Chemotherapy for MTX-LPD is selected according to that for de novo LPD, although the strategy for aggressive P-LPD and non-specific LPD is not well established. The absolute lymphocyte count in the peripheral blood has been suggested as a candidate marker for MTX-LPD development and RRE. Several clinical issues, including correct diagnosis among overlapping clinicopathological features in MTX-LPD and clinical management of LPD by ISDs other than MTX, require further investigation.

Immune response in LPD during methotrexate administration (MTX-LPD) in rheumatoid arthritis patients

“…8 Histopathology and immunophenotype, genetics and clinical characteristics, clinicopathological features, and clinical management of MTX-LPD are well summarized in other reviews. 68,69 The proportion of DLBCL in RA-LPD was approximately 60%, being higher than that in the general population (30-40%). 67,70 Another study found that DLBCL was predominant in RA-LPD before the widespread use of MTX, including in untreated RA patients.…”

Methotrexate-associated lymphoproliferative disorder demonstrating composite lymphoma of EBV-negative diffuse large B-cell lymphoma and EBV-positive mucocutaneous ulcer

“…The first point is the importance of multiple biopsy for MTX-LPD. MTX-LPD are mainly DLBCL and CHL, but rarely FL, 9 peripheral T-cell lymphoma, 8 etc. The pathological features are different, but all cases have the potential for tumor regression by MTX withdrawal.…”

“…8 On the other hand, clinical features of DLBCL vary, and EBV-negative cases more often require immunochemotherapy. 9 There are many predictive factors for tumor regression other than pathological features and EBV positivity such as T cell subset in peripheral blood, 11 absolute lymphocyte count after MTX withdrawal, 12 and serum lactate dehydrogenase, C-reactive protein, and soluble interleukin-2 receptor levels. 13 This case followed a different pattern of tumor regression.…”

Potential mechanisms of spontaneous regression in patients with B-cell lymphoma; the significance of co-stimulatory molecules in lymphoma cells

“…Traumatic stress or injury including biopsy is considered to be a trigger for SR, and occasionally, administration of corticosteroids, anti-lymphoma drugs, or infection may cause the initiation of SR. [1][2][3] We propose a possibility that, after Fig. 2.…”

“…1 SR is currently of interest for many clinicians because of an increased number of methotrexate-related lymphoproliferative disorders, and because SR is observed in many patients after withdrawal of methotrexate. 2 In terms of a mechanism, anti-tumor immune responses by host T lymphocytes reacting against tumor cells are believed to be involved in SR, 3 and several cases have recently been reported. In a recent issue of journal of clinical and experimental hematopathology (JCEH), Tanaka et al described a case of diffuse large B-cell lymphoma (DLBCL) with SR. 4 A 35-year-old man had multiple mesenteric lymphadenopathy and a thickened small intestine wall, and was diagnosed with DLBCL (germinal center origin) without infection with Epstein-Barr virus (EBV) following laparoscopic lymph node biopsy.…”