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.