Bridging to Second Allogeneic Peripheral Blood Stem Cell Transplantation with Nelarabine in a Patient with Multiply Relapsed/Refractory T-Cell ALL

T-cell acute lymphoblastic leukemia (ALL) is a very challenging disease to attain durable remission once relapses. We treated a 40 year-old female with T-cell ALL, normal cytogenetic who relapsed twice after her matched related donor allogeneic stem cell transplantation (allo-SCT) with Nelarabine achieving third complete remission prior to second allo-SCT. She was initially treated with HyperCVAD x 5 cycles with IT chemo (negative cytopathology). After achieving complete remission (CR), she received PK-directed IV Busulfan and Fludarabine myeloablative conditioning followed by 12/12 HLA-MRD allo-SCT with 11.06 x 10⁶ CD34+cells/kg. GVHD prophylaxis was Tacrolimus and mini-Methotrexate (5 mg/m²/dose). She engrafted on time. She never had GVHD. On day+ 100, bone marrow biopsy revealed relapsed disease involving 60% of marrow space. Patient was treated with one cycle augmented HyperCVAD resulted in second CR. She developed elevated transaminases, liver biopsy was consistent with NASH and drug-induced liver injury, negative for GVHD. She was given alpha interferon 3 million units MWF in attempt to induce GVHD/GVL while pending insurance approval for donor lymphocyte infusion. She developed full donor chimerism as well as extensive chronic GVHD involving skin, liver, skin, lung, eyes, vagina, and mouth after interferon. She was treated only with topical steroid therapies and remained in CR until day+266. On Day+266, she was again found to have relapse of her disease with significant leukocytosis and circulating blasts. CT scan showed recurrent large anterior mediastinal mass. She was treated with Cytoxan (500 mg/m²) and Etoposide (100 mg/m² x 5 days), complicated with neutropenic fevers before receiving outpatient Nelarabine. She recovered with progressive leukemia, which was treated with a single dose of Cytoxan 600mg/m². She developed diffuse alveolar hemorrhage, treated in the MICU with high dose steroids and antimicrobials. She was discharged to outpatient clinic and given Nelarabine at 1500 mg/m² on days +1, +3, +5, every 3 weeks for 2 cycles. Her clinical condition and peripheral counts improved with disappearing peripheral blasts after the initial cycle of Nelarabine. She received second cycle and subsequent restaging studies showed remission marrow (CR-3) with complete resolution of mediastinal mass on CT scan. She developed mild neuropathy after Nelarabine. She is currently inpatient receiving her for second MRD allo-SCT. This case is noteworthy and clearly illustrates lack of GVL effect in T-cell ALL and an efficacy of two cycles of Nelarabine even in the setting of refractory T-cell ALL relapsing twice after allogeneic SCT.