Marrow Transplant Recipients Research Articles

HLA donor-specific antibodies in allogeneic hematopoietic stem cell transplantation: challenges and opportunities.

Allogenic hematopoietic stem cell recipients may have preformed antibodies directed against foreign HLA antigens. The use of partially HLA-mismatched allogeneic hematopoietic stem cell donors allows for the possibility of the presence of circulating HLA donor-specific antibodies (DSAs) in the recipient. The presence of DSAs at the time of stem cell infusion increases the risk of primary graft failure. More recently developed technology using solid phase immunoassays (SPIs) with fluorochrome-conjugated beads has greatly improved the ability to detect and classify DSAs. When used in combination with the classic lymphocytotoxic complement-dependent and flow cytometric crossmatch tests, SPIs help provide DSA strength assessment. Parous females frequently harbor DSAs. DSAs tend to be of higher intensity when directed against haploidentical first-degree relatives. DSA assessment requires frequent monitoring as their relative strength can change over time. Although the criteria that constitutes a prohibitive DSA is unknown, desensitization techniques can result in engraftment rates as experienced in fully HLA-matched allogeneic blood or marrow transplantation recipients.

Biology of the BKPyV: An Update.

The BK virus (BKPyV) is a member of the Polyomaviridae family first isolated in 1971. BKPyV causes frequent infections during childhood and establishes persistent infections with minimal clinical implications within renal tubular cells and the urothelium. However, reactivation of BKPyV in immunocompromised individuals may cause serious complications. In particular, with the implementation of more potent immunosuppressive drugs in the last decade, BKPyV has become an emerging pathogen in kidney and bone marrow transplant recipients where it often causes associated nephropathy and haemorrhagic cystitis, respectively. Unfortunately, no specific antiviral against BKPyV has been approved yet and the only therapeutic option is a modulation of the immunosuppressive drug regimen to improve immune control though it may increase the risk of rejection. A better understanding of the BKPyV life cycle is thus needed to develop efficient treatment against this virus. In this review, we provide an update on recent advances in understanding the biology of BKPyV.

Dynamics of B Cell Recovery In Kidney/Bone Marrow Transplant Recipients

Previous studies identified B cell gene signatures and predominance of specific B cell subsets as a marker of operational tolerance after kidney transplantation. These findings suggested a role for B cells in the establishment or maintenance of tolerance. Here we analyzed B cell recovery in 4 subjects, 3 of whom achieved tolerance after combined kidney/bone marrow transplantation. Peripheral B cell subsets were examined longitudinally by flow cytometry. Immunoglobulin heavy chain repertoire analysis was performed using next-generation sequencing. Lastly, the patients' serum reactivity to HLA was assessed by Luminex. B cell counts recovered approximately 1 year posttransplant except for 1 subject who experienced delayed reconstitution. This subject resumed immunosuppression for acute rejection at 10 months posttransplant and underwent preemptive retransplantation at 3 years for chronic rejection. B cell recovery was accompanied by a high frequency of CD20 + CD24CD38 transitional B cells and a diversified clonal repertoire. However, all 4 subjects showed prevalence of CD20 + CD27+ memory B cells around 6 months posttransplant when B cell counts were still low and the clonal B cell repertoire very limited. The predominance of memory B cells was also associated with high levels of somatically mutated immunoglobulin heavy chain variable sequences and transient serum reactivity to HLA. Our observations reveal the presence of memory B cells early posttransplant that likely escaped the preparative regimen at a time consistent with the establishment of tolerance. Further studies are warranted to characterize the functional properties of these persisting memory cells and evaluate their potential contribution to tolerance induction.

A Case of the nephrotic syndrome in bone marrow transplantation recipient, histologically showing overlapped glomerular lesions of thrombotic microangiopathy and membranous nephropathy

Nephrotic syndrome (NS) rarely occurs in post-hematopoietic stem cell transplantation (HSCT) recipients but represents the renal manifestation of graft-versus-host disease (GVHD). Membranous nephropathy (MN) accounts for almost two thirds of post-HSCT NS and is caused by immune complex deposition. Renal thrombotic microangiopathy (TMA) without fulfillment of clinical criteria for TMA has been underreported because of reduced opportunity for histological examination. However, renal TMA has recently been reported in association with GVHD and humoral immunological reactions. Although both MN and TMA after HSCT are associated with GVHD and immunological abnormalities, these diseases are exceptionally coexistent in renal biopsy specimens. We herein describe a case of post-HSCT NS, histologically showing overlapped lesions of TMA and MN. Renal biopsy specimen after presentation of NS revealed early stage MN and TMA with evidence of chronicity. TMA was thought to have preceded MN, and renal biopsy at the phase of pre-nephrotic proteinuria might reveal earlier histological changes of isolated renal TMA. Detection of subclinical renal TMA earlier by spontaneous renal biopsy can help prevent progression of renal injury or overlapping of other renal pathologies. We also demonstrated Th2 predominant intraglomerular infiltration of lymphocytes by immunohistochemistry.

Growth, bone and muscle mass are adversely affected in bone marrow transplant recipients: a body composition analysis

Growth, bone and muscle mass are adversely affected in bone marrow transplant recipients: a body composition analysis

Abstract 1126: Potent inhibition of HCMV by modulating the cellular SNARE syntaxin 5

Abstract Human cytomegalovirus (HCMV), also referred to as human herpesvirus-5 (HHV-5), can cause serious and even fatal disease in immunocompromised individuals and newborns, namely individuals with AIDS, solid organ transplant recipients, chemotherapy patients and recipients of bone marrow and stem cell transplants. HCMV is a ubiquitous virus found throughout all geographic regions and socioeconomic groups, infecting greater than 50% of adults in industrialized countries and as many as 100% in developing countries. Although current therapeutics improves clinical outcomes, they are limited by toxicity, intravenous infusion and the development of resistance by the virus. Thus, there is a pressing need to develop novel therapeutics to prevent HCMV infections with concomitant organ toxicity. Formation of the cytoplasmic viral assembly compartment (cVAC) is an important step for efficient HCMV assembly. To do this, the virus must alter and repurpose the normal cellular balance of membrane and protein flux, a process that is not well understood. We have identified a compound Retro94, which potently inhibits production of infectious HCMV virions in cells by operating against a host cell process, rather than directly targeting the virus. The presence of Retro94 results in the severely impaired production of infectious virions, as great as 5 logs (99-99.99%). Here we discuss in vitro, in vivo, stability, and binding study of Retro94. Overall, our findings have identified Retro94, as novel agent that affects key cellular trafficking factors important for supporting HCMV infection. Citation Format: Dhimant H. Desai, Linda Cruz, Nicholas T. Streck, Trisha D. Desai, Aron Lukacher, Shantu G. Amin, Nicholas J. Buchkovich. Potent inhibition of HCMV by modulating the cellular SNARE syntaxin 5 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1126. doi:10.1158/1538-7445.AM2017-1126

Epidemiology of polyomavirus BK (BKV) and the emergent African variant in kidney and bone marrow transplant recipients in the Fundacion Valle del Lili in Cali, Colombia

To describe the epidemiology of BKV and to assess the presence of the African variant in bone marrow and kidney transplant patients who have suspected BKV reactivation. A descriptive study was conducted, using institutional records, at the Fundación Valle del Lili, Cali-Colombia. The overall prevalence of BKV during the study period was 51%. The African variant was identified in 49.4% of samples that were positive for BKV. 50.6% of the samples were found to have the wild strain of BKV. Among BKV positive patients, 57% were kidney transplant recipients and 43% were bone marrow transplant recipients. This is the first epidemiological study describing the African variant of BKV in Colombia.

Compassionate use experience with high-titer respiratory syncytical virus (RSV) immunoglobulin in RSV-infected immunocompromised persons.

Respiratory syncytial virus (RSV) may cause fatal lower respiratory tract infection (LRTI) in immunocompromised patients. Ribavirin with or without standard intravenous immunoglobulin (IVIG) is frequently given although efficacy is debated. Infusion of IVIG with high levels of neutralizing antibody against RSV may offer benefit in these patients. RI-001 contains standardized levels of high-titer anti-RSV neutralizing antibody and was provided for compassionate use to 15 patients with RSV LRTI who either failed conventional therapy or had significant risk of progression. Patients were treated on day 1 with RI-001 1500mg/kg, followed 2days later with 750mg/kg. Pre- and post-infusion sera were measured for RSV neutralizing antibody. Patient data were analyzed for safety related to infusion of RI-001, and clinical outcomes. Patients ranged in age from 2months to 71years and 80% had hematologic malignancy or were bone marrow or hematopoietic stem cell transplant recipients. Administration was well tolerated. Pre-infusion neutralizing titers ranged from 51 to 1765 geometric mean titer (mean 646±519) and all patients demonstrated at least a 4-fold rise (mean 6410±4470) 5-10days post infusion. Eleven of 15 improved and were discharged from the hospital. Days from positive RSV test to RI-001 treatment was shorter in survivors compared to non-survivors (4.4±2.8 vs. 20.3±21.0days, P=.02). Administration of RI-001 was well tolerated and resulted in significant increases in serum neutralizing antibody titers to RSV. Our data suggest that early identification of RSV and treatment with RI-001 may offer benefit.

263 - A Retrospective Examination of Issues Addressed during Music Therapy Sessions with Bone Marrow Transplant Recipients

263 - A Retrospective Examination of Issues Addressed during Music Therapy Sessions with Bone Marrow Transplant Recipients

Bone marrow mesenchymal stromal cells induce nitric oxide synthase-dependent differentiation of CD11b+ cells that expedite hematopoietic recovery.

Bone marrow microenvironment is fundamental for hematopoietic homeostasis. Numerous efforts have been made to reproduce or manipulate its activity to facilitate engraftment after hematopoietic stem cell transplantation but clinical results remain unconvincing. This probably reflects the complexity of the hematopoietic niche. Recent data have demonstrated the fundamental role of stromal and myeloid cells in regulating hematopoietic stem cell self-renewal and mobilization in the bone marrow. In this study we unveil a novel interaction by which bone marrow mesenchymal stromal cells induce the rapid differentiation of CD11b+ myeloid cells from bone marrow progenitors. Such an activity requires the expression of nitric oxide synthase-2. Importantly, the administration of these mesenchymal stromal cell-educated CD11b+ cells accelerates hematopoietic reconstitution in bone marrow transplant recipients. We conclude that the liaison between mesenchymal stromal cells and myeloid cells is fundamental in hematopoietic homeostasis and suggests that it can be harnessed in clinical transplantation.

Severe community-acquired adenovirus pneumonia treated with oral ribavirin: a case report

BackgroundAdenovirus is a common pathogen of acute upper respiratory infection in children and is generally self-limiting. Severe adenovirus infections have been reported in immunocompromised hosts especially bone marrow transplantation recipients due to hematologic malignancy. Severe adenovirus pneumonia in immunocompetent hosts has rarely been reported and optimal treatment has not been established. We report a case of community-acquired severe adenovirus pneumonia which was successfully treated with early administration of oral ribavirin.Case presentationA 39 year-old, previously healthy Korean male was admitted with symptoms of cough, myalgia, febrile sensation. Laboratory findings revealed that he had hypoxemia, thrombocytopenia and elevated transaminase. Chest imaging showed a consolidation with pleural effusion, which was rapidly progressed. All microbiological tests were negative except multiplex real-time reverse transcriptase polymerase chain reaction using respiratory specimen, which was positive for human adenovirus. Under the diagnosis of severe adenovirus pneumonia, we started oral ribavirin, which results in complete recovery without any complications.ConclusionsThis case demonstrates that oral ribavirin, instead of other expensive antiviral treatment, could be a good therapeutic option for the severe adenovirus pneumonia at least occurred in immunocompetent hosts.

Genetic testing and counseling of a recipient after bone marrow transplant from a sibling harboring a germline BRCA1 pathogenic mutation.

Allogenic bone marrow transplant recipients represent a unique challenge, when they are referred for genetic testing and counseling. When performing genetic testing, it is extremely important to ensure that the detected DNA mutations originate from the patients own DNA, and therefore the most appropriate and reliable biological sample for DNA isolation must be obtained. The aim of the present study was to present the germline testing and counseling approach utilized in a rare case of a chimeric woman who received an allogenic bone marrow transplant from a sibling with a germline BRCA1 pathogenic mutation. According to our results, hairs with follicles are a reliable and ready source of DNA in a patient whose blood is of allogenic bone marrow transplant donor origin. Compared with a fibroblast culture, which is more difficult to obtain, the hair follicles are much more accessible and hair sampling is less invasive for the patient. Genetic testing based on the other sources of DNA, such as buccal swabs, is questionable due to the known risk of donor DNA contamination.

Determination Of Prior Educational Needs Of Bone Marrow Transplantation Recipients İn Our Society

Determination Of Prior Educational Needs Of Bone Marrow Transplantation Recipients İn Our Society

Phase I Clinical Trial Evaluating Abatacept in Patient with Steroid-Refractory Chronic Graft Versus Host Disease

Introduction: Chronic graft versus host disease (cGVHD) remains a major source of morbidity and mortality following allogeneic transplantation. While corticosteroids remain first line therapy for cGVHD, they are associated with significant toxicity, and a substantial proportion of patients fail to completely respond. Treatments for steroid-refractory cGVHD are limited. While the pathophysiology of chronic GVHD is complex, activated T cells play a critical role, driven by allo-antigen stimulation. As such, inhibition of T cell activation via blockade of co-stimulation has potential as a therapeutic target in cGVHD. Abatacept is a recombinant fusion protein consisting of the extracellular domain of human CTLA-4 and a fragment of the Fc domain of human IgG1 that has been modified to prevent complement fixation and antibody-dependent cellular cytotoxicity. Abatacept is the first drug in a class of agents termed "selective co-stimulation modulators." The CTLA-4 moiety of Abatacept binds specifically to CD80 and CD86 and down-modulates the CD28-mediated co-stimulation of T cells. We conducted a phase I clinical trial was conducted to evaluate the safety, clinical and immune effects of Abatacept in patients with steroid-refractory cGVHD.Methods: The study followed a 3+3 design with two escalating doses of Abatacept to determine the maximum tolerated dose (MTD): 3 mg/kg and 10 mg/kg. Dose-limiting toxicities (DLTs) were defined as Grade 3 or 4 toxicities judged to be probably or definitely related to Abatacept. Infection was not considered a DLT. Abatacept was administered for a total of 6 doses. Doses 1-3 were administered at two-week intervals. One month following Dose 3, Abatacept was given at four-week intervals for three doses (Doses 4-6). Inclusion criteria included recipients of allogeneic bone marrow or stem cell transplantation with myeloablative or reduced intensity conditioning, with cGVHD defined by NIH consensus criteria. Patients must have had treatment with ≥ 0.5 mg/kg/day of prednisone for at least 4 weeks. Patients with active malignant disease relapse or other active malignancy and patients with uncontrolled infection were excluded. Peripheral blood was drawn prior to each dose of Abatacept and following completion of therapy to assess the effect of treatment on circulating T cells. PD-1 expression on circulating T cells, and T cell expression of interferon gamma versus IL-10 was assessed by multichannel FACS analysis.Results: 17 subjects were treated. Three patients were treated at a dose of 3 mg/kg without DLT. Three evaluable patients completed treatment on cohort 2, at a dose of 10mg/kg without DLT. A forth participant withdrew consent following one dose of treatment and therefore is not evaluable. Ten patients were treated on an expansion cohort at a dose of 10mg/kg. We observed one grade 4 pulmonary infection, and three grade 3 pulmonary infections which resolved. Other Abatacept related adverse events included grade 2 gastritis (n=1), grade 2 pain (n=1), and grade 1 diarrhea (n=2), fatigue (n=2), rash (n=1), and skin pain (n=1). Of the 16 evaluable patients, 7 (44%) achieved a clinical partial response as defined by improvement of two disease systems based on the 2011 NIH consensus criteria. Abatacept resulted in a 51.3% reduction in prednisone usage in clinical responders with a mean baseline dose of 27mg compared to a mean dose of 14mg 1 month following the 6th dose of Abatacept (p = 0.01). PD-1 expression on circulating CD4+ and CD8+ T cells increased from a mean of 3.4% and 2.7% respectively at baseline to a mean of 8.9% and 7.6% respectively at one month following the 6thdose of Abatacept in clinical responders (n=3; p<0.05). In contrast, no change in T cell expression of PD-1 was observed in non-responders. A shift from Th1 to Th2 cytokine secretion was observed in clinical responders, with a mean 2.8 fold decrease in interferon gamma and a mean 2.5 fold increase in IL-10 secretion by circulating T cell populations (n=4).Conclusion: Abatacept is well-tolerated in the treatment of steroid-refractory cGVHD. Abatacept resulted in the improvement in NIH cGVHD scores in 44% of patients with steroid-refractory GVHD with a significant decrease in prednisone dose. An increase in PD-1 expression and a skewing toward Th2 cytokines was observed in clinical responders. Based on this promising data, a phase II trial is being initiated. DisclosuresSoiffer:GentiumSpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Arnason:Gilead: Consultancy. Avigan:Astex: Research Funding; DCPrime: Research Funding. Rosenblatt:Astex: Research Funding; BMS: Research Funding; DCPrime: Research Funding.

Checkpoint Inhibitor Therapy and Graft Versus Host Disease in Allogeneic Bone Marrow Transplant Recipients of Haploidentical and Matched Products with Post-Transplant Cyclophosphamide.

Background: Concerns have been raised whether immune checkpoint inhibitor therapy in the alloBMT setting will result in graft versus host disease (GvHD) and transplant related mortality (TRM). We report our experience with a variety of checkpoint inhibitors used before or after allogeneic bone marrow transplantation (alloBMT). Our series comprises patients who received T cell-replete hematopoietic stem cells from HLA-haploidentical or -matched donors and is limited to those treated with post-transplant cyclophosphamide (PTCy) as primary GvHD prophylaxis.Patient selection: We retrospectively reviewed the records of alloBMT recipients who received PTCy and received checkpoint inhibitor therapy before or after alloBMT. GvHD was assessed using the CIBMTR GVHD index.Results:Eleven patients received checkpoint inhibitor therapy prior to alloBMT: anti-PD-1: Nivolumab n=6, anti-CTLA4: Ipilimumab n=8 (3 patients received both nivolumab and ipilimumab). These patients received a median of 4 (range 1 - 18) cycles of therapy. The median interval from last checkpoint inhibitor treatment to day of transplant was 43 (range 18-302) days. All patients received nonmyeloablative conditioning; 6 received partially mismatched allografts (5 were HLA haploidentical). Four patients developed Grade II aGvHD: Three patients who had received partially mismatched allografts (haplo-2, 9/10 unrelated-1) experienced stage 3 cutaneous GvHD only; one patient who received a 10/10 unrelated donor allograft developed stage 3 cutaneous GvHD with stage 1 liver involvement. Three patients were on immunosuppression when GvHD developed, the fourth patient with cutaneous and liver GvHD had been taken off tacrolimus on day 68 due to concerns of graft failure. GvHD resolved with treatment in each case. None of these patients developed chronic GvHD and none have died [median follow-up of 0.66 (range 0.91 - 2.0) years post alloBMT].Nine patients received checkpoint therapy following alloBMT: anti-PD-1: Pembrolizumab n = 1, Nivolumab n= 6, anti-CTLA4: Ipilimumab n= 3 (one patient received nivolumab and ipilimumab). Eight patients had received nonmyeloablative conditioning; 5 received haploidentical allografts. Six received treatment for relapse of their hematologic malignancy, 1 for relapsed pediatric sarcoma, and 2 for newly diagnosed lung cancer. The median time to initiation of checkpoint inhibitor therapy was 1.2 (range: 0.8 - 5.8) years post alloBMT. Patients received a median of 5 (range 1 - 24) cycles of therapy. There was 1 case of Grade II aGvHD; stage 3 cutaneous GvHD when DLI from a 10/10 matched unrelated donor was given for relapsed disease after ipilimumab. This resulted in GvHD which was not accompanied by the desired graft-vs-leukemia effect. There were no other cases of acute or chronic GvHD in this group. There were 4 tumor-related deaths: pediatric sarcoma (1), lung cancer (1), and AML (2). The median follow-up for this group is 2 years (range 0.85 - 8.0) post alloBMT.Conclusions: In this small series, the incidence and severity of GvHD seen in patients who received checkpoint inhibitors was similar to that seen in patients treated with PTCy as GvHD prophylaxis without checkpoint inhibitors. GvHD was seen in patients treated with checkpoint inhibitors prior to alloBMT, but was generally mild and readily controlled and there were no associated deaths. In patients treated with checkpoint inhibitors after alloBMT, the only case of GvHD occurred after the patient received DLI. We caution that use of checkpoint inhibitors in closer temporal proximity to transplant might well be associated with increased risk of GvHD or severity of GvHD. [Display omitted] DisclosuresBorrello:WindMIL Therapeutics: Equity Ownership, Patents & Royalties, Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding. Wagner-Johnston:Seattle Genetics: Research Funding. Smith:Celgene: Consultancy, Other: member of DSMB.

African American Race Is a Newly Identified Risk Factor for Postengraftment Blood Stream Infections in Pediatric Allogeneic Blood and Marrow Transplantation

Blood stream infections (BSI) are a major source of morbidity and mortality both in allogeneic blood and marrow transplant (BMT) recipients. Various risk factors for BSI in BMT have been identified. The impact of race and cytomegalovirus (CMV) viremia, a common complication after engraftment, however, has not been rigorously assessed. This is important because both CMV infection and ganciclovir, the mainstay of pre-emptive therapy, have myelosuppressive and immunosuppressive effects. We conducted a retrospective analysis to test the hypothesis that race and CMV viremia predispose allogeneic BMT patients to postengraftment BSI. We analyzed 278 allogeneic BMT performed at Children's Healthcare of Atlanta between January 1, 2005 and December 31, 2014 that met eligibility criteria. We performed a multivariate analysis to estimate the effect of CMV viremia on risk for BSI in the postengraftment period (days +30 to 100). Risk for BSI was associated with CMV viremia (hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.51 to 7.36; P = .003); grade III and IV acute graft-versus-host disease (HR, 3.28; 95% CI, 1.55 to 6.92; P = .002), and African American race (HR, 2.22; 95% CI, 1.09 to 4.51; P = .027). The results of our study highlight the importance of a novel risk factor for postengraftment BSI, not previously considered—African American race.

Estimating the Size of the U.S. Population at Risk of Severe Adverse Events from Replicating Smallpox Vaccine.

To quantify the population at risk of serious adverse reactions to replicating smallpox vaccine. Conditions known or suspected to carry risk were identified via Centers for Disease Control and Prevention planning documents, other federal publications, and peer-reviewed literature. Conditions identified were categorized as historically recognized risks or more recently recognized immunocompromised states that may pose risk. Major historical risk factors were as follows: eczema/atopic dermatitis, pregnancy, HIV, and primary immunodeficiency. More recently identified states were as follows: rheumatoid arthritis, inflammatory bowel disease, dialysis, bone marrow transplant recipients within 24months post-transplant, solid-organ transplant recipients within 3months post-transplant, age under 1year, and systemic lupus erythematosus. The estimated prevalence or absolute number of affected individuals for each condition was ascertained from peer-reviewed studies, vital statistics, and registry databases. An estimated 48,121,280 to 50,028,045 individuals (15.2-15.8% of the U.S. population) are potentially contraindicated to replicating smallpox vaccine. This rises to 119,244,531 to 123,669,327 (37.4-38.8%) if household contacts are included. These figures are significant and larger than the only previously published study. Understanding this number allows for improved clinical utilization, equitable attention to the health needs of a vulnerable population, and strategic vaccine stockpiling.

Graft Transit Time Has No Effect on Outcome of Unrelated Donor Hematopoietic Cell Transplants Performed in Australia and New Zealand: A Study from the Australasian Bone Marrow Transplant Recipient Registry

A previous study found that platelet recovery and mortality were worse in recipients of myeloablative bone marrow transplants where graft transit times were longer than 20 hours. This retrospective study of unrelated myeloablative allogeneic transplantation performed within Australia and New Zealand analyzed transplant outcomes according to graft transit times. Of 233 assessable cases, 76 grafts (33%) were sourced from bone marrow (BM) and 157 (67%) from peripheral blood. Grafts sourced from Australia and New Zealand (47% of total) were associated with a median transit time of 6 hours versus 32 hours for overseas sourced grafts (53% of total). Graft transit temperature was refrigerated in 85%, ambient in 6%, and unknown in 9% of cases, respectively. Graft transit times had no significant effect on neutrophil or platelet engraftment, treatment-related mortality, overall survival, and incidence of acute or chronic graft-versus-host disease. Separate analysis of BM grafts, although of reduced power, also showed no significant difference in either neutrophil or platelet engraftment or survival between short and longer transport times. This study gives reassurance that both peripheral blood stem cell and especially BM grafts subjected to long transit times and transported at refrigerated temperatures may not be associated with adverse recipient outcomes.

Primary Lung Adenocarcinoma as Secondary Malignancy After Bone Marrow Transplantation

SESSION TITLE: Student/Resident Case Report Poster - Lung Cancer I SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Bone marrow transplant (BMT) recipients have a higher risk of developing secondary malignancies. Majority of secondary malignancies are cutaneous or oral mucosal cancers. Secondary cancers most often occur late, usually after 100 days from transplantation. Death caused by malignant neoplasm less than 5 years after transplantation is rare. We report a case of adenocarcinoma of the lung presenting as a secondary malignancy 71 days after bone marrow transplantation. CASE PRESENTATION: 54 year old Female in remission from Stage IV low grade follicular Non-Hodgkins Lymphoma underwent a matched sibling donor allogenic stem cell transplant for acute lymphoblastic lymphoma. She was treated with fludarabine and melphalan conditioning therapy as well as tacrolimus for graft vs host disease (GVHD) prophylaxis and presented 71 days following BMT as a transfer with dyspnea. Previous positron emission tomography (PET) showed resolving but persistent hypermetabolic ground glass opacifications in the right lower lobe thought to be resolving infectious/inflammatory process. Few months prior, computed tomography of chest revealed stable bilateral pulmonary micronodules without lymphadenopathy. On physical examination the patient was afebrile, tachypnic and tachycardic. Pulmonary auscultation revealed decreased right breath sounds and rhonchi. Chest X-ray revealed large right pleural effusion. The patient subsequently developed acute respiratory failure requiring intubation and diagnostic and therapeutic thoracentesis. Pleural fluid cytology was positive for adenocarcinoma consistent with lung primary. Despite best efforts, patient’s respiratory status continued to deteriorate and patient passed away in intensive care unit. DISCUSSION: Although BMT is a successful and recognized treatment option for malignant hematologic disorders, patients have increased risk for secondary malignancies. Conditioning chemotherapy, radiation therapy and immunosuppression therapy for GVHD increase secondary malignancy risk by mechanisms of direct organ toxicity and depletion of lymphocyte tumor regulation. Our patient developed a secondary malignancy as an unusual early complication of BMT after chemotherapy conditioning and GVHD prophylaxis with an aggressive primary lung adenocarcinoma. PET scan is known to poorly detect adenocarcinoma in situ and minimally invasive adenocarcinoma. Early stage malignancy may have been already present and overlooked. Further immunosuppression in context of BMT may have provided an environment for proliferation and rapid progression of disease. CONCLUSIONS: We report a rare presentation of lung adenocarcinoma as an early BMT complication. Due to profound immunosuppression, malignancy in BMT patients can present quickly and aggressively. Thorough follow up is needed for any resolving hypermetabolic states seen on PET scan. Reference #1: Bhatia, Smita, et al. “Solid cancers after bone marrow transplantation.” Journal of Clinical Oncology 19.2 (2001): 464-471. DISCLOSURE: The following authors have nothing to disclose: Tasneem Kaleem, Jordan Ray, John Moss, Laura Finn No Product/Research Disclosure Information

Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy.

BackgroundTo help decide when to start and when to stop pre-emptive therapy for cytomegalovirus infection, we conducted two open-label randomized controlled trials in renal, liver and bone marrow transplant recipients in a single centre where pre-emptive therapy is indicated if viraemia exceeds 3000 genomes/ml (2520 IU/ml) of whole blood.MethodsPatients with two consecutive viraemia episodes each below 3000 genomes/ml were randomized to continue monitoring or to immediate treatment (Part A). A separate group of patients with viral load greater than 3000 genomes/ml was randomized to stop pre-emptive therapy when two consecutive levels less than 200 genomes/ml (168 IU/ml) or less than 3000 genomes/ml were obtained (Part B). For both parts, the primary endpoint was the occurrence of a separate episode of viraemia requiring treatment because it was greater than 3000 genomes/ml.ResultsIn Part A, the primary endpoint was not significantly different between the two arms; 18/32 (56%) in the monitor arm had viraemia greater than 3000 genomes/ml compared to 10/27 (37%) in the immediate treatment arm (p = 0.193). However, the time to developing an episode of viraemia greater than 3000 genomes/ml was significantly delayed among those randomized to immediate treatment (p = 0.022). In Part B, the primary endpoint was not significantly different between the two arms; 19/55 (35%) in the less than 200 genomes/ml arm subsequently had viraemia greater than 3000 genomes/ml compared to 23/51 (45%) among those randomized to stop treatment in the less than 3000 genomes/ml arm (p = 0.322). However, the duration of antiviral treatment was significantly shorter (p = 0.0012) in those randomized to stop treatment when viraemia was less than 3000 genomes/ml.DiscussionThe results illustrate that patients have continuing risks for CMV infection with limited time available for intervention. We see no need to alter current rules for stopping or starting pre-emptive therapy.