Pediatric EBV-negative monomorphic post–solid organ transplant lymphoproliferative disorders [EBV(-)M-PTLD]: Characteristics, treatment, and outcome from 11 pediatric academic centers.
Authors: Afify Zeinab A.M. , Taj Mary , Srivatsa Kavitha , Miller Tamara P. , Edington Holly , Dalal Mansi , Robles Joanna , Ford James , Ehrhardt Matthew J. , Ureda Tonya. , Rubinstein Jeremy , McCormack Sarah , Rivers Julia M. , Chisholm Karen M. , Kavanaugh Madison. , Bukowinski Andrew J. , Friehling Erika , Marks Lianna , Smith Christine Moore , Mason Clinton 
Published: June 2022

10012

Background: Pediatric EBV(-)M-PTLD comprises < 15% of M-PTLD. Two-year-overall survival of pediatric EBV(+) PTLD is 83%. No large multi-institution pediatric-specific reports are available for EBV(-)M-PTLD. Methods: Retrospective study of characteristics, treatment, and outcome of pediatric solid organ recipients diagnosed with EBV(-)M-PTLD at age ≤21 years (y) in 11 pediatric transplant centers in US and UK. Results: Thirty-three patients transplanted with solid organs between 1991-2017 developed EBV(-)M-PTLD. Twenty-two (66%) were male. Median age (range) at organ transplantation was 2.6y(0.1-17), diagnosis of EBV(-)M-PTLD 14y(3-20), interval from transplant to PTLD 8.3y (2.3-18). Transplanted organs were heart (n = 10), kidney (n = 17), liver (n = 4), small bowel (n = 1), liver and small bowel (n = 1). Immunosuppressive therapy at the time of diagnosis of PTLD was available on 31 patients. All were receiving a calcineurin inhibitor except one who was on sirolimus alone. Tacrolimus was given in 27 patients, alone (n = 3), or in various combination with mycophenolate (n = 8), azathioprine (n = 9), prednisone (n = 8), or everolimus (n = 1). Four of these receiving tacrolimus received 3 immunosuppressive drug combinations. Cyclosporine was given in 3 patients, with mycophenolate (n = 1), prednisone (n = 1), or both (n = 2). Murphy stages were I (n = 1), II (n = 7), III (n = 22), and IV (n = 3). Lactate dehydrogenase was elevated in 19/31 (61%) and > 2X upper limit of normal in 10/31 (32%) tested. Pathological diagnoses were diffuse large B-cell lymphoma (n = 30) and B-NHL NOS (n = 3). Treatment included: rituximab alone (n = 1), low-dose cyclophosphamide, prednisone, and rituximab (CPR; n = 9), pediatric mature B-NHL-specific regimen [FAB/LMB with (n = 12) or without (n = 1) rituximab], EPOCH-R (n = 2), R-CHOP (n = 3), modified R-CHOP (n = 2), COP (n = 1), and R-COP (n = 2). At a median 2.9y (0.3-11y) from diagnosis, 26/33 (79%) were alive and in complete remission (CR). Three experienced relapses at 1, 3, and 6.5y after CPR, rituximab alone, and B-NHL therapy, respectively. All achieved a sustained second CR with additional B-NHL therapy. Of the 7 deaths: 6 were from progressive disease despite escalation to intensive B-NHL therapy following initial COP (n = 1), R-COP (n = 1), CPR (n = 2), and B-NHL therapy (n = 2), and one cardiac transplant recipient from presumed cardiotoxicity. There was one graft rejection that was successfully treated. Conclusions: This collaboration represents the first multi-institution series of pediatric EBV(-)M-PTLD. Overall survival was comparable to that reported for pediatric EBV(+) PTLD, but inferior to DLBCL in immunocompetent children. These preliminary data reflect a wide range of therapeutic regimens used over 20 years and strongly support an organized collaborative effort to collect data prospectively.