Incidence of and Risk Factors for Cytomegalovirus (CMV), Epstein Barr Virus (EBV) and Adenovirus (ADV) Reactivation in Pediatric Recipients Post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHCT)

Evelyn Rustia, Leah Violago, Zhezhen Jin, Monica Bhatia, Andrew Kung, Marc Foca, Diane George, James Garvin, Prakash Satwani
2014 Biology of Blood and Marrow Transplantation  
Intrathecal (IT) chemotherapy can be given to patients with acute leukemia post hematopoietic stem cell transplant (HSCT) in an attempt to prevent relapse in the central nervous system (CNS). We performed a retrospective analysis of 166 patients with acute leukemia who underwent first HSCT at Memorial Sloan-Kettering Cancer Center between 1999 and 2013. Patients who were not eligible for post HSCT IT prophylaxis due to graft-versus-host disease or acute transplant related complications were
more » ... uded from the analysis. Indication for HSCT included acute lymphoblastic leukemia (ALL) (n¼115), acute myeloid leukemia (n¼45) or acute biphenotypic leukemia (n¼6). The median age of patients was 10.7 years (range 0.6-27.5). Disease status at transplant included CR1 (38%), CR2 (44%) and not in remission (4%). Donor grafts underwent ex vivo T cell depletion in 67% (110) of patients, and 71.6% (116) of patients received their graft from an unrelated donor. Conditioning therapy included TBI in 76% of cases. Patients with a history of CNS disease (36%) were included in this analysis; these patients received CNS radiation either during induction therapy or as a boost prior HSCT. Monthly post-transplant IT prophylaxis was administered to 71% of patients, starting at 2 months post HSCT. Prophylaxis consisted of IT cytarabine +/-hydrocortisone, with patients with no prior CNS disease receiving 5 doses post HSCT and those with previous CNS disease receiving 11 doses. The rate of overall relapse at 2 years was 33.2% for the entire cohort, with a CNS relapse rate of 5.4%. The CNS relapse rate at 2 years for patients with ALL was 7.1%, and only 1 patient with AML developed CNS relapse. In subset analysis, patients with ALL who received IT prophylaxis post HSCT had a significantly lower rate of CNS relapse compared to those that did not (4.4% vs 17.3%, P ¼ 0.04). Our study demonstrates that monthly IT prophylaxis with cytarabine +/hydrocortisone post HSCT may be beneficial for patients with acute lymphoblastic leukemia in the prevention of CNS relapse. 92 Reduced-intensity conditioning (RIC) regimens are increasingly used to reduce transplant-related mortality (TRM) for pediatric patients (pts) undergoing hematopoietic cell transplantation (HCT) for nonmalignant diseases. However, these pts are at increased risk for post-transplant mixed donor/ recipient chimerism (MC) and/or primary and secondary graft failure (GF). Intervention with donor lymphocytes (DLI) or second transplants may be necessary, but there is limited information about timing and results of intervention. We retrospectively evaluated 31 consecutive pediatric recipients of an alemtuzumab-based RIC HCT at the Children's Hospital of Philadelphia from May 2007 to December 2012 to determine the incidence of MC and GF, and timing of interventions. All pts received alemtuzumab (Campath) with either fludarabine (150mg/m 2 )/melphalan (140 mg/m 2 ) (n¼30) or fludarabine/busulfan (n¼1). The timing of Campath differed according to disease. Pts with hematologic disorders and IPEX received Campath beginning day -21 or -22. Pts with hemophagocytic lymphohistiocytosis (HLH) received proximal (N¼8) or intermediate (n¼2 ) Campath starting at day -9 or -13, respectively. Diagnoses included HLH in 10 pts, hemoglobinopathy in 8 pts, primary immunodeficiency in 8 pts, and bone marrow failure in 5 pts. All grafts were unmanipulated bone marrow from matched sibling donors (45%), matched unrelated donors (52%) or mismatched related donor (3%). Donor chimerism was evaluated using polymerase chain reaction of microsatellite markers/short tandem repeats at regular intervals post-transplant. Four pts died of TRM (n¼3) or early disease progression (n¼1) and were not included in the analysis. Of the 27 surviving pts, 18 (66.7%) displayed MC (donor chimerism <100%) on at least one occasion, with 12 (44.4%) reaching a nadir MC level <80%. Two pts with MC80% experienced recurrent disease, one with HLH and one with auto-immune syndrome. Of the 12 pts with nadir MC<80%, 6 received DLI with 2 subsequent GFs. Of the remaining 6 pts who did not receive DLI, there were also 2 GFs. The overall incidence of GF/recurrence was 22.2% (6/27). Within the HLH group 7/7 surviving pts developed MC, with 5 (71.4%) reaching a nadir <80%. Despite DLI/boost in all 5 of these pts, 2 progressed to GF. The incidence of GF/recurrence in the surviving HLH pts was 42.9% (3/7) By contrast, in the non-HLH pts, only 11 of 20 (55.0%) surviving pts developed MC with 7 (35.0%) reaching a nadir<80%. Of these 7 with MC<80%, 2 progressed to GF for an overall incidence of GF/ recurrence of disease of 15% (3/20). In summary, we observed a high incidence of MC and GF in recipients of Campath-based RIC, particularly in HLH pts. The role for DLI/boost in preventing GF in pts receiving RIC HCT for non-malignant disease who experience low/falling MC requires further study. Viral infections are associated with significant morbidity and mortality following AlloHCT. There are no established guidelines for the frequency of viral monitoring and only a few studies in children have analyzed the impact of viremia on AlloHCT related outcomes. In 2008, our center created a standard operating procedure of prospective PCR monitoring for CMV, EBV and ADV prior to AlloHCT and then weekly for 180 days post AlloHCT. Abstracts / Biol Blood Marrow Transplant 20 (2014) S72eS90 S84
doi:10.1016/j.bbmt.2013.12.106 fatcat:3z2xpgcyc5h3hl52coq7kzl7iq