Discussion:
PBL is a rare type of high-grade B-NHL, frequently involving extra nodal sites(1). Our patient had multiple extra-nodal site sites of involvement at presentation (ovary, breast, adrenal gland, vertebra and para-vertebral soft tissue) An important differential diagnosis for PBL is plasmablastic myeloma. Absence of bone marrow involvement with abnormal plasma cells, or myeloma related end-organ dysfunction makes plasmablastic myeloma an unlikely diagnosis (3). We reviewed literature and found that CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like regimens like Hyper-CVAD-MA (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, and high-dose methotrexate and cytarabine), CODOX-M/ IVAC (cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ ifosfamide, etoposide, and high-dose cytarabine), COMB (cyclophosphamide, oncovin, methyl-CCNU, and bleomycin), and infusional EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) have been used (4). Polychemotherapy achieves more than 50% complete remissions (CRs) in patients with disseminated disease (2). Though the role of infusional EPOCH has not been proven effectively, its use is supported by the impressive results achieved in HIV-associated Non-Hodgkin’s Lymphoma. This has become the treatment of choice in many institutions (5) . Short series have been reported on the role of AHCT in both HIV and immunocompetent patients.  A multi-center Phase II GIGAT group study included 5 patients with PBL, among other lymphoma types, who underwent an AHCT after first CR. Four of them maintained CR after 13–83 months (6) . Considering the aggressive course, PBL patients with high-risk features should be considered for consolidation with AHCT in first-line setting (7) . Our patient received daEPOCH chemotherapy and was consolidated with AHCT in CR1. She remained in remission for 1 year and 4 months, which is consistent with the median overall survival (OS) reported elsewhere (8) . Factors affecting survival in PBL are the following: achieving complete remission (CR), performance status, clinical stage, MYC gene rearrangements, and International Prognostic Index (9) . Our patient relapsed in the breast in Jan 2017 and had insignificant response to 3 cycles of salvage chemotherapy (DHAP). She was started on bortezomib and lenalidomide (VR). A literature review by Guerrero-Garcia TA et al, on the use of bortezomib along with chemo regimens in PBL patients observed higher response and survival rates in the frontline setting, and impressive transient responses in relapsed cases (10) . Other agents like lenalidomide, brentuximab vedotin, and Interleukin 6 directed agents have been shown to benefit in PBL in a few case reports (11, 12) . Few case reports of daratumumab, an antibody directed against CD38, have shown activity in patients with relapsed PBL (13). Daratumumab was added along with VR from cycle 3. After 4 cycles of combination DaraVR and Radiation therapy, PET CT was in cMR. There are very few cases of successful AlloHCT in PBL in HIV positive patients (14) . She underwent an AlloHCT with haplo-identical sibling brother. She developed limited gut and skin GVHD which responded to steroids. She is alive now 4 years post diagnosis of PBL and more than 2 years post AlloHCT with no evidence of disease, and is off immunosuppression. The emergence of biology driven approaches like novel B-cell targets and immunotherapeutic approaches like cellular immunotherapy (CD30 directed CAR T-cell); anti-PD-1 or anti-PDL-1 monoclonal antibodies; EBV directed antiviral agents (arginine butyrate, ganciclovir), bromodomain extra terminal (BET) inhibitor for MYC gene positive cases; and PI3K/Akt/m-TOR pathway inhibitors hold promise (15) . This case exemplifies the fact that when clinical compulsions push treating teams to explore options other than the conventionally tried methods in a hard to treat cancer, outcomes can be rewarding occasionally. This patient received both conventional and novel therapies, and was later consolidated with a haploidentical AlloHCT.