In contrast, a 30% ORR was reported for single-agent MTX in the treatment of LGLL and PRCA, which is lower than that for CTX (47%) and CsA (55%).25 The pathophysiology of PRCA in LGLL is thought to involve LGLs inhibiting erythropoiesis, chronic antigenic stimulation from infections or autoimmune diseases, and immune processes.26 Cytokines such as TNF released by LGLs may inhibit hematopoiesis and contribute to PRCA in LGLL. Here, TNF is linked to pure red-cell aplasia.