scholarly journals 5: Long-Term Follow-Up of Administration of Donor-Derived EBV-Specific CTLs to Prevent and Treat EBV Lymphoma After Hemopoietic Stem Cell Transplant

2008 ◽  
Vol 14 (2) ◽  
pp. 3 ◽  
Author(s):  
G.A. Hale ◽  
M. Pule ◽  
P. Amrolia ◽  
H. Weiss ◽  
C. Bollard ◽  
...  
Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3350-3350
Author(s):  
Roberto Cairoli ◽  
Luigi Mancini ◽  
Giambattista Bertani ◽  
Maria Luisa De Angelis ◽  
Nadia Vantaggiato ◽  
...  

Abstract Abstract 3350 Introduction: In the absence of serum hepatitis B (HB) surface antigen (HBsAg) and clinical evidence of HB, an occult HB virus (HBV) infection (OBI) is defined as the existence of HBV DNA in the serum, in the peripheral blood mononuclear cells (PBMC), and/or in the liver. Most frequently, OBI follows the resolution of acute hepatitis and continues indefinitely after HBsAg clearance and liver function improvement. Usually, this form of infection, termed secondary OBI (sOBI), is associated with the presence of serum anti-HB core antibodies (anti-HBc). Up to 20% of individuals with OBI do not react for either anti-HBc or any other serological indicator of HBV exposure. Consistent with the woodchuck model, this form of infection, termed primary OBI (pOBI), is characterized by the presence of DNA in both serum and PBMC, but not in the liver. Although reactivation of sOBI has been reported in a high proportion of hemopoietic stem cell transplant (HSCT) recipients, pOBI reactivation risk has not yet been fully investigated in the transplant setting. We followed up 9 long term surviving HSCT recipients with pOBI, in order to define its clinical significance in immune suppressed patients. Patients and Methods: A total of 75 consecutive patients with hematological disease, receiving autologous or allogeneic HSCT between April 2006 and March 2007, were included in a database and retrospectively examined. As a prerequisite for inclusion in the study, each of the following was needed: (i) negative serological indicators of HBV exposure and absence of clinical signs/symptoms of hepatitis at the time of HSCT, (ii) positive HBV DNA, as detected by polymerase chain reaction (PCR), in both serum and PBMC samples drawn within 6 months before transplant, and (iii) availability of stocked frozen serum/PBMC samples collected after HSCT from each patient. Following these criteria, 9 patients (7 males, 2 females) were selected for the analysis. Five patients (1 Hodgkin disease, 3 non-Hodgkin lymphomas, and 1 B-cell chronic lymphocytic leukemia) received autologous HSCT, and 4 patients (1 acute myeloid leukemia, 1 multiple myeloma, 1 myelodysplastic syndrome, and 1 acute lymphoblastic leukemia) received allogeneic HSCT. Median age at transplant was 49 (range: 33–63) years. No patient received lamivudine prophylaxis. Serum and PBMC samples collected after HSCT were analyzed for HBV serology and DNA detection. The latter was performed by in-house PCR amplification by nested primers (detection limit 50 copies/ml) from highly conserved S region encompassing a-determinant of HBV. Direct sequencing of all HBV DNA amplified products was used to confirm the specificity of the reaction. Results: In 8 cases, one serum/PBMC sample per patient was available, at a median of 27 (range: 21–34) months after HSCT; in 1 case, three serum/PBMC samples were available, at 17, 22, and 28 months after HSCT, respectively. During follow-up, positive HBV DNA was found, both in the serum and in the PBMC. All patients were confirmed to be infected with HBV subgenotype D1, with mutations known to impair HBsAg antigenicity. Three patients were confirmed to be further infected with HBV subgenotype A2. So far, 41 to 52 months after transplant (median: 46 months), neither patients showed seroconversion nor developed clinical hepatitis, suggesting pOBI persistence. Conclusions: Although the virus persisting in pOBI remains biologically competent, it is likely neither to reach liver-pathogenic doses nor to induce “classical” HBV reactivation during PBMC-restricted replication. However, prospective studies with large sample size and long-term follow-up are warranted, to define the actual clinical relevance of HBV occult infection. Indeed, OBI with low viremia could induce DNA damage, cellular demise, immune hypo-responsiveness, and oxidative stress in peripheral blood lymphocytes. Disclosures: No relevant conflicts of interest to declare.


2017 ◽  
Vol 23 (3) ◽  
pp. S410-S411
Author(s):  
Jaskiran Kaur ◽  
Madhu Ragupathi ◽  
Alysa Pleiner ◽  
Luda Kushner ◽  
Mostafizur Rahman ◽  
...  

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19028-e19028
Author(s):  
Stephanie Hoffman ◽  
Pavan Reddy ◽  
John Martin Magenau ◽  
Attaphol Pawarode ◽  
Brian Parkin ◽  
...  

e19028 Background: Long-term complications of COVID-19 in hematopoietic stem cell transplant (HCT) recipients are unknown. Recent studies have described short term outcomes of COVID-19 infection post allogeneic (allo) and autologous (auto) HCT. In this study we provide long term follow-up of the outcomes of COVID-19 infection in allo and auto HCT recipients. Methods: We performed a retrospective study of adult patients who have received allo or auto HCT and were subsequently diagnosed with COVID-19 infection between March-December 2020. We summarized patient characteristics, laboratory and treatment data related to COVID-19 infection in these patients. Results: In this study, we provide long-term follow-up of over 7 months. Fifteen patients were identified for inclusion (allo n = 12, auto n = 3). Median follow-up was 7.8 months (range 1.9-10.7) for surviving patients. Median age at COVID-19 diagnosis was 55 years (range 24-77). Most patients were > 1 year out from transplant (allo n = 10, auto n = 1, 73%). Two patients (allo n = 1, auto n = 1, 13%) had undergone transplant within the preceding month. Most allo patients (n = 11, 73%) had received myeloablative conditioning. At the time of COVID-19 diagnosis, 9 allo patients (75%) were on immunosuppression (IS) (n = 7 for chronic graft-versus-host-disease (GVHD); n = 2 for GVHD prophylaxis). Eleven patients (73%) required hospitalization (allo n = 9, auto n = 2). Per the National Institutes of Health definitions of COVID-19 illness severity, 3 patients had critical disease (allo n = 2, auto n = 1, 20%), 5 severe (allo n = 5, 33%), 3 moderate (allo n = 2, auto n = 1, 20%), and 4 mild (allo n = 3, auto n = 1, 27%). All patients with chronic GVHD required hospitalization. Two patients died (allo n = 1, auto n = 1, 13%)—both had critical COVID-19 infections, were > 65 years old, > 3 years out from transplant, and had significant comorbidities. The allo patient was receiving prednisone < 1 mg/kg for chronic lung GVHD at COVID-19 diagnosis. Two allo patients developed either acute GVHD or chronic GVHD exacerbation within 3 months of their infection. One patient developed biopsy-proven acute GVHD (max grade III) 3 weeks after her infection and another patient developed a severe exacerbation of chronic GVHD within 3 months—both continue to require multi-modal IS. The remaining 7 patients with chronic GVHD have been maintained on either stable or tapered IS. Conclusions: Given the effect of COVID-19 infection, its impact on HCT recipients is important to define. The majority of HCT patients who contracted moderate-critical COVID-19 infections in our study were either on IS or had significant comorbidities. Our observational data points to the importance of long-term follow-up in HCT patients. Future studies are needed to delineate whether there is a relationship between COVID-19 infection and GVHD development or exacerbation. The role of vaccination in HCT recipients remains to be explored.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3996-3996 ◽  
Author(s):  
Adam Bryant ◽  
Elizabeth Pringle ◽  
Christopher Bredeson ◽  
David S. Allan ◽  
Grizel Anstee ◽  
...  

Abstract Myasthenia Gravis is an antibody-mediated disease that affects the neuromuscular junction. Despite advances in immune-targeted therapies, a subset of patients demonstrate refractory disease with severe or life-threatening symptoms. Disease control has been achieved using autologous hematopoietic stem cell transplant (HSCT) in a variety of autoimmune conditions including multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, stiff person syndrome, and others. Here we report our center’s experience using autologous HSCT in seven patients with myasthenia. Seven myasthenia patients underwent HSCT between 2001 and 2011. Six patients were female. Median age (range) was 37 at diagnosis (17-52) and 43 at HSCT (24-55). Before HSCT, myasthenia severity, standardized by the Myasthenia Foundation of America (MGFA) clinical classification, was graded as moderate in 2 patients, severe in 3 patients, and life-threatening in 2 patients. Treatment regimens included pyridostigmine in all patients, and immune-targeted therapies including: steroid therapy in all patients, an additional immunomodulating drug in 6 patients, and plasma exchange or intravenous immunoglobulin in all patients. All patients had at least one myasthenia-related emergency department visit or hospitalization prior to HSCT, 3 requiring ICU stays and 2 requiring intubation. All patients underwent HSCT mobilization with cyclophosphamide and filgrastim. Stem cells were harvested from peripheral blood and selected for CD34+ cells in all cases. Conditioning regimens used busulfan, cyclophosphamide, and antithymocyte globulin (Bu-Cy-ATG) in 4 patients, Cy-ATG and total body irradiation in 2 patients, and etoposide, melphalan and dexamethasone in 1 patient who was undergoing HSCT for relapsed follicular lymphoma (FL). Median post-HSCT follow-up was 40 months (range 29-149). At last follow-up MGFA postintervention status was classified as complete stable remission (CSR) in all patients, indicating patients bad been experiencing no myasthenia symptoms and were on no myasthenia therapy for at least one year. Six patients had no further hospitalizations or emergency department visits post HSCT. One patient required hospitalizations in the 6 months post HSCT but at time of writing had been not hospitalized for myasthenia for more than 10 years. One patient died 29 months post HSCT from relapsed FL. At time of death this patient’s myasthenia was in CSR. There were no HSCT regimen-related deaths. No patients required ICU care during HSCT admission. Absolute neutrophil count exceeded 0.5 x 109/L on median post HSCT day 11 (range 13 - 28). Median hospital stay, including administration of conditioning regimen was 34 days (range 20-43). In the first post-HSCT year the cohort experienced 6 viral reactivations in 3 patients: 3 cases CMV viremia, 1 case BK virus-induced hemorrhagic cystitis, 1 case VZV dermatitis, 1 case oral HSV. Two late post-HSCT complications were observed: one case of acquired amegakaryocytic thrombocytopenia (post-HSCT day 701), and one case of relapsed FL (post-HSCT day 846) resulting in patient death. HSCT resulted in longstanding symptom- and treatment-free remission in seven patients with refractory myasthenia gravis. The procedure was tolerable however the intense immune depletion transiently increased risk of viral reactivation. This experience demonstrates that in selected myasthenia gravis cases, HSCT is a viable option for long-term disease control. The novel application of HSCT for this and other autoimmune conditions is an area that warrants further exploration and long-term follow-up. Disclosures No relevant conflicts of interest to declare.


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