Generation of Epstein Barr Virus Specific Cytotoxic T Lymphocytes (EBVCTLs) Resistant to the Immunosuppressive Drug Tacrolimus (FK506)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3536-3536
Author(s):  
Biagio De Angelis ◽  
Gianpietro Dotti ◽  
Concetta Quintarelli ◽  
Leslie E Huye ◽  
Lan Zhang ◽  
...  
Keyword(s):  
Immunosuppressive Agents ◽  
Retroviral Vector ◽  
Immunosuppressive Drugs ◽  
Thymidine Uptake ◽  
Solid Organ ◽  
Cell Transplant ◽  
Antigen Specificity ◽  
Hematopoietic Stem ◽  
Post Transplant

Abstract Adoptive transfer of autologous EBV-CTLs to hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients is a safe and often effective means for prevention and treatment of EBV-associated post transplant lymphoproliferative disorders (PTLD). Although immunosuppressive drugs can be tapered in patients developing PTLD, they often cannot be completely withdrawn because of the risk of graft rejection, a particular concern in lung, heart or liver transplant recipients. These immunosuppressive drugs may limit the expansion, persistence and efficacy of transferred EBV-CTLs. One of the most widely used immunosuppressive agents is FK506 whose effects are highly dependent on binding FKBP12 proteins, since T cells generated from FKBP12 knockout mice are completely resistant to the inhibitory effects of FK506. We have generated EBV-CTLs resistant to FK506 by knocking down FKBP12 using a small interfering RNA (siRNA) stably expressed from a retroviral vector. After extensively screening potential target sequences, we identified one, designed as siRNA4, that knocks down >90% of FKBP12 protein expression in T cell lines and also in EBV-CTLs, as assessed by Western blotting. We then generated two retroviral vector encoding for siRNA4/eGFP and irrelevant siRNA/eGFP, respectively. These vectors were used to transduce established EBV-CTL lines generated from 7 EBV-seropositive donors. Transduction efficiency was 46.3±22.5% and 55.4±27.5% for siRNA4 and irrelevant-siRNA, respectively. We measured the proliferation of transduced CTLs in the presence of FK506, in short term and long term cultures. Using a thymidine uptake assay, we found that the inhibiton of proliferation by increasing concentrations of FK506 was significantly diminished in siRNA4+ CTLs compared to control CTLs (41±4% inhibition for siRNA4+ CTLs vs 74± 2% for control CTLs). To evaluate the effects of knocking down FKBP12 in long-term cultures, control and siRNA4+ CTLs were stimulated weekly with the antigen (autologous EBV-LCL) with or without the addition of FK506 (5ng/ml) and low dose IL-2 (20U/mL). We found that the proportion of siRNA4+ CTLs increased over time not only as a percentage of GFP+ cells (from 46±22% to 89.4±5.3% after 5 stimulations) but also numerically (median fold expansion: 34.3, range 5–60). In contrast, control EBV-CTLs did not show any selection in culture, since the percentage of GFP+ cells remained unchanged (from 56±27% to 57±23.1%) and CTLs ceased to proliferate (median fold expansion: 2, range 0–5). Finally, we found that siRNA4+ CTLs retained their antigen specificity, having MHC-restricted cytotoxic activity against EBV-targets (66±22% vs 16±12% for autologous and allogenic LCL, respectively at an E:T ratio of 20:1 for siRNA4+ CTLs; 61±12% vs 15±12% for autologous and allogenic LCL, respectively, for control CTLs). Modified CTLs also maintained their production of IFNγ in response to specific EBV-peptides, as assessed by ELIspot assays. We are currently evaluating the in vivo expansion of genetically modified EBV-CTLs in the presence of FK506. In conclusion, we have developed a strategy that produces EBV-CTLs resistant to FK506. This strategy may be beneficial to improve EBV immune reconstitution in patients at high risk of developing post transplant lymphoma.

Long-Term Survival In Patients With Acute Steroid Refractory Graft-Versus-Host-Disease (SR-GVHD) Treated With Infliximab Combined With Daclizumab

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4624-4624
Author(s):  
Sanaz Nicky Soltani ◽  
Ramaprasad Srinivasan ◽  
Theresa Jerussi ◽  
A. John Barrett ◽  
Thomas E Hughes ◽  
...  
Keyword(s):  
High Probability ◽  
Chronic Gvhd ◽  
Complete Response ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Survival ◽  
Post Transplant

Acute SR-GVHD occurs in approximately 15% of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), and is associated with a 70-90% long-term mortality rate. We previously reported that concomitant blockade of TNF-α and IL-2 pathways with infliximab combined with daclizumab have a synergistic therapeutic effect, with a high probability of complete resolution of SR-GVHD. Although various treatment modalities are effective in the treatment of SR-GVHD, minimal long-term follow up data exists for complete responders to second line treatments. Here we report long-term outcomes in a cohort of 23 subjects developing SR-GVHD treated with infliximab/daclizumab. A consecutive series of 141 patients with a variety of hematological and non-hematological malignancies as well as nonmalignant hematological disorders including severe aplastic anemia (SAA), paroxysmal nocturnal hemoglobinuria and pure red cells aplasia, underwent a reduced intensity allogeneic HSCT from an HLA identical or single antigen mismatched relative at a single institution between 2/2001 and 12/2008. Transplant conditioning consisted of cyclophosphamide (60 mg/kg days -7, -6) and fludarabine (25 mg/m2days -5 to -1) with or without equine ATG or 6-12 Gy of total body irradiation. GVHD prophylaxis was with cyclosporine with or without additional MMF or MTX. Twenty three patients (median age 35 years, range 13-65 years) developed SR-GVHD at a median of 28 days post transplant. SR-GVHD was defined as absence of response to at least 6 days of high dose methylprednisolone therapy. Following a diagnosis of SR-GVHD, patients received a combination of daclizumab (1mg/kg given on days 1, 4, 8, 15, 22), infliximab (10mg/kg given on days 1, 8, 15, 22), broad spectrum bacterial and anti-fungal prophylaxis, and had their methylprednisolone tapered to 1mg/kg/day. Combined cytokine blockade was highly active against SR-GVHD, with 21/23 (87.5%) patients achieving a complete response (CR), defined as total resolution of GVHD in all involved organ systems. All complete responders survived to hospital discharge. With a median follow-up of 9 years (range 5-10 years), 9/23 (39%) survive, including 6 patients without chronic GVHD whose immunosuppressive therapy (IST) has been discontinued and 3 patients with chronic GVHD (2 limited and 1 extensive) who continue to be tapered off IST. Fourteen of 21 patients with resolution of SR-GVHD died a median 173 days post transplant (range 67-1039 days), including 1 from complications related to recurrent SR-GVHD, 6 from progression of malignancy (all solid tumors), 2 from bleeding related to peptic ulcer disease and 5 from infectious complications including invasive fungal infection and CMV disease. A subgroup analysis showed 5/6 patients with SAA developing SR-GVHD had a complete response to combined infliximab/daclizimab. Remarkably, at a median 6 years follow up, 67% (4/6) of these SAA patients were long-term survivors. All these survivors have maintained normal blood counts and remained transfusion independent with 100% donor chimerism in myeloid and T-cell lineages. Conclusion Patients with SR-GVHD treated with infliximab combined with daclizumab had a high probability of achieving a complete response with nearly 40% of patients having long-term survival. This is the first report to show that long-term survival can be achieved in a substantial proportion of patients receiving combined IL-2 and TNF blockade for SR-GVHD. Disclosures: Off Label Use: Infliximab is FDA approved for the treatment of psoriasis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis and ulcerative colitis. Daclizumab gained FDA approval for use in transplant rejection.

Malignancy Following Solid Organ and Hematopoietic Stem Cell Transplantation

2009 ◽  
Vol 02 ◽  
pp. 49
Author(s):  
Angela Susanne Punnett ◽  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Immunosuppressive Agents ◽  
Solid Organ ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Increased Risk

There is a growing appreciation of the increased risk for malignancy following solid organ and hematopoietic stem cell transplantation as the survival of these patient populations increases overall. The risk for malignancy is related to a complex interaction of type, degree, and duration of immunosuppression, viral status, and recipient age. Most of the malignancies documented are common in the general population but occur with increasing incidence and have significant implications for post-transplant surveillance. Post-transplant lymphoproliferative disorder is specific to the transplant population and remains a treatment challenge. The development of novel immunosuppressive agents, the use of individualized immunosuppressive regimens, and collaborative therapeutic trials are necessary to advance clinical care for these patients. This article will review the current issues around malignancy in the post-transplant patient population.

scholarly journals 1393. Tuberculosis (TB) After Solid-organ Transplant (SOT) and Hematopoietic Stem Cell Transplant (HSCT)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S506-S506
Author(s):  
Cecilia F Peña-Puga ◽  
Oscar Morado-Aramburo ◽  
Darwin Lambraño-Castillo ◽  
Jennifer Cuellar-Rodríguez
Keyword(s):  
Clinical Characteristics ◽  
Clinical Symptoms ◽  
First Year ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Latent Tb ◽  
Disseminated Disease

Abstract Background Tuberculosis is an important opportunistic infection that affects transplant recipients; the risk of active infection increases significantly when compared with the general population. Most disease results from reactivation of latent infection, being extrapulmonary and disseminated disease the most common presentations. Most cases occur during the first year post-transplantation when immunosuppression is higher. We describe the clinical characteristics of patients diagnosed with TB after transplant. Methods Single-center, retrospective study of adult SOT and HSCT recipients in Mexico City, who developed active TB after transplant. We reviewed medical records, and collected demographic data, clinical characteristics, and outcome. Results We identified 16 patients with post-transplant TB; 13 SOT, and 3 HSCT recipients. The majority of SOT recipients were women (53.8%); median age was 43 years, 9 were kidney and 4 liver transplant recipients. At TB diagnosis, 84.6% of patients were on 3 immunosuppressors. Latent TB was assessed before transplant in 5 patients (38.4%), of these 3 (60%) were tuberculin skin test+, and 2 received isoniazid. Extrapulmonary disease was most common (7, 53.8%). Predominant symptoms were fever (53.8%), chills (30.8%), and diaphoresis (38.5%); six were diagnosed during the 1st year (46.2%) post-transplant; the median of time to diagnosis was 24 months after transplant. The diagnosis was made by histopathology in most cases. Twelve patients received first-line anti-TB treatment. Overall mortality was 30.8%, directly attributable to TB in 2. In the HSCT group, 2 were women; median age was 22 years, 2 allogeneic and 1 autologous transplant. One patient had been treated for latent TB before transplantation. Two developed disseminated disease. Two patients presented within 6 months after the transplant, and the other within a year. Mortality was 100%, attributable to the infection in two patients. Conclusion In regions with intermediate to a high prevalence of TB; post-transplant TB could result from reactivation or post-transplant exposure. Most cases occur within the first year post-transplant; clinical symptoms are nonspecific, which lead to a delay in diagnosis. Morbidity and mortality remains high. Disclosures All authors: No reported disclosures.

Survival outcomes of post-transplant lymphoproliferative disorder: A 12-year analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19543-e19543
Author(s):  
Hira Ghazal Shaikh ◽  
Rafiullah Khan ◽  
Michael Grabel ◽  
Roman Jandarov ◽  
Mahmoud Charif ◽  
...  
Keyword(s):  
Poisson Regression ◽  
Lymphoproliferative Disorder ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Solid Organ ◽  
Cell Transplant ◽  
Annual Income ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Post Transplant

e19543 Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare and potentially fatal complication of chronic immunosuppression in solid organ transplant (SOT) and hematopoietic stem cell transplant recipients. With an overall incidence of ̃ 1 percent in the transplant recipients, it is the most common malignancy, with the exception of skin cancer, after SOT in adults. There is a paucity of information concerning the outcomes and prognostic indicators of PTLD. Methods: We queried the National Cancer Database (NCDB) from 2004 – 2015 for patients with diagnosis of PTLD. Overall survival (OS) was calculated from the date of diagnosis to the date of last contact or death using Kaplan Meier curves to present the cumulative probability of survival. Additionally, Poisson regression was used to test the association between baseline variables and days to event. All statistical analyses were performed using R 4.0.3. Results: Total number of patients identified by inclusion criteria was 425. 1-year OS was 73% (CI 0.684, 0.776), 3-year OS 63% (CI 0.581, 0.683), and 5-year OS 56% (CI 0.502, 0.619) in patients with survival data available (n = 365). 263 patients were excluded due to incomplete data, yielding a final cohort of 192 patients for correlational analysis. The median age was 59 years. Majority were males (60%), < 65 year old (75.5%), Hispanics (91%), and had Charlson-Deyo Comorbidity score of 0 (63.5%). 77% were Caucasians while 15.6% were African Americans. OS was longer in males, Caucasians, patients who received radiation (versus no radiation), those treated at academic or comprehensive cancer center (versus community cancer center), had annual income > $63000 (versus < $63000) by Poisson regression analysis, however the difference was not statistically significant. Conclusions: Our data demonstrates a trend toward poor survival with socioeconomic and treatment variables including gender, race, annual income, treatment center expertise and radiation treatment. Randomized trials are needed to further assess the outcomes of PTLD.

scholarly journals Non-Destructive Post-Transplant Lymphoproliferative Disorder Shows Distinct Clinical Features with HHV-6 Reactivation in a Subset

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2792-2792
Author(s):  
Samuel Yamshon ◽  
Miguel Dario Cantu ◽  
Ethel Cesarman ◽  
Sarah C. Rutherford ◽  
Amy Chadburn ◽  
...  
Keyword(s):  
New York ◽  
Human Herpesvirus ◽  
Clinical Information ◽  
Causative Role ◽  
Solid Organ ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Tissue Diagnosis ◽  
Non Destructive

Background: Post-transplant lymphoproliferative disorders (PTLD) are a diverse group of lymphoid neoplasms arising after solid organ (SOT) or hematopoietic stem cell transplant (HSCT). They may resemble lymphomas in immunocompetent patients (monomorphic); present as destructive, heterogeneous lesions (polymorphic); or be non-destructive but mass-forming (non-destructive, previously known as 'early lesions'). PTLDs are often associated with Epstein-Barr virus (EBV) infection or reactivation, which likely functions as a driver in these cases. Non-destructive lesions may be challenging to diagnose in the absence of EBV. However, a significant fraction of PTLDs are EBV(-), including a subset of non-destructive lesions. The pathogenesis of these remains to be fully elucidated. Human herpesvirus 6 (HHV-6) reactivation is common during transplantation, occurring in up to 70% of HSCT and 80% of SOT patients. While it has been hypothesized that HHV-6 may play a role in PTLD, particularly in EBV(-) cases, the role of HHV-6 in the pathogenesis of PTLD remains underexplored. Methods: Following IRB approval, pathology archives at Weill Cornell/New York Presbyterian Hospital were searched to identify patients with a tissue diagnosis of PTLD and correlated with clinical information. A tissue microarray was constructed from blocks with sufficient tissue. Standard immunohistochemistry (IHC) and in situ hybridization for EBV-encoded RNA (EBER) were performed, and IHC conditions were optimized for antibodies against HHV-6 gp60/110 (Millipore Sigma, MAB853) and p41 (Santa Cruz Biotechnologies, 9A5D12). Statistical comparisons utilized Student's t-test and Fisher's exact test. Results: We identified 79 patients from 6/23/94-6/6/19 with a tissue diagnosis of PTLD. Morphologic subtype could be determined in 74, including 8 patients with non-destructive lesions. Compared to monomorphic or polymorphic, patients with non-destructive PTLDs were significantly younger (median age 9, p<0.01) and more likely status post heart transplant (5/8 cases, p<0.001, Table 1). By contrast, polymorphic PTLDs occurred relatively more frequently in HSCT patients (25/33 cases, p<0.01). All morphologic subtypes were frequently EBV+ (63-88%) but EBV positivity was greater in polymorphic than monomorphic lesions (p<0.05). While tissue testing failed on blocks > 20 years old, 13 PTLD cases from 12 patients had sufficient evaluable material for HHV-6 testing (Table 2). 9/12 patients had a SOT (8 renal, 1 heart) and 3 had HSCT. HHV-6 was identified in 5/13 lesions (38%), all of which were in SOT patients (Figure 1). EBER was detected in 8/13 lesions (62%). When stratified by PTLD subtype, 3/3 non-destructive PTLDs were HHV-6+ (100%). Two were EBER(-) and the remaining case only showed scattered EBER+ cells. Unfortunately, material was not available for testing the EBER+ non-destructive lesions. 2/9 of the monomorphic lesions tested (22%) were positive for both HHV-6 and EBER. While the series is limited, the association between HHV-6 and non-destructive lesions, compared to other types of PTLD, appears significant (p<0.05). EBV did not appear to be associated with HHV-6 status (p = 0.29). Conclusions: Non-destructive, monomorphic and polymorphic PTLDs show significant differences in timing, patient demographics and transplant type, suggesting that they may differ in associated risk factors affecting their pathogenesis. Confirming prior studies, we find non-destructive lesions tend to occur in younger patients, often following SOT as compared to HSCT and with a median time from transplantation of ~50 months. In addition, the presence of HHV-6 in the absence of (or with limited) EBV in the 3 non-destructive lesions tested raises the possibility that HHV-6 may play a role in the pathogenesis of this PTLD subtype that has yet to be defined. These findings are intriguing given the frequent reactivation of HHV-6 seen in transplant populations. HHV-6 has been variably associated with post-transplant complications including pneumonitis, delayed hematopoietic engraftment and graft versus host disease and thus received relatively more attention in the HSCT population. A causative role for HHV-6 in PTLD remains speculative, but these findings raise the possibility that clinicians treating the SOT population should also consider aggressively identifying and treating HHV-6 reactivation. Disclosures Rutherford: AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Heron: Consultancy, Honoraria; Janssen Scientific Affairs: Consultancy, Honoraria; Juno Therapeutics Inc: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals 1394. Clinicopathologic Features of Infectious and Noninfectious Tissue Granulomas in Transplant Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S506-S507
Author(s):  
Eliezer Zachary Nussbaum ◽  
Rita Abi Raad ◽  
Maricar Malinis ◽  
Marwan M Azar
Keyword(s):  
Risk Factors ◽  
Organ Transplant ◽  
Severe Infection ◽  
Adverse Outcomes ◽  
Solid Organ ◽  
Cell Transplant ◽  
Clinicopathologic Features ◽  
Hematopoietic Stem ◽  
Cryptogenic Organizing Pneumonia ◽  
Post Transplant

Abstract Background There is a paucity of literature about the implications of granulomatous disease in hematopoietic stem cell transplant (HSCT) and solid-organ transplant (SOT) patients. Given the broad range of infectious and noninfectious etiologies as well as the heightened risk for severe infection, it is important to characterize the clinicopathologic features of granulomas in this population and to develop a framework to guide further evaluation. Methods We performed chart reviews of 1,280 transplant recipients (791 SOT and 489 HSCT) at Yale-New Haven Hospital from 2009 to 2019 to identify patients with granulomas in pathologic specimens obtained peri-transplantation. Data on histopathology, microbiology, indication for biopsy, patient characteristics, and clinical presentation were recorded. Morbidity and mortality were noted at 1, 3, and 12 months after granuloma diagnosis. Results We identified 28 patients with granulomas (9 SOT, 19 HSCT); an incidence of 2.2%. None had explicit risk factors for MTB. Most granulomas (93%) were non-necrotizing. Common sources were lung (n = 9) and lymph node (n = 5). Most were found post-transplant (n = 19) and biopsies were prompted mostly by symptoms (n = 13) or incidental imaging findings (n = 9). Most granulomas were not associated with an infectious process (n = 20). Among infectious granulomas, bacterial soft-tissue infection (n = 2), bartonellosis (n = 2), and fungal infection (1 Cryptococcus and 1 Blastomyces) were most common. MTB PCR was negative in 4 specimens. Among granulomas discovered in SOT patients, 44% were infectious compared with 21% in HSCT recipients. Most infectious granulomas were found in symptomatic patients (75%). One granuloma-related adverse outcome occurred in a case of cryptogenic organizing pneumonia discovered pre-HSCT that worsened with tapering of immunosuppression post-HSCT. Conclusion Granulomas were uncommon in a large transplant population. Most were deemed noninfectious and their presence alone was not associated with adverse outcomes post-transplant or with increased immunosuppression. Granulomas were more likely to be infectious in SOT recipients and those with symptoms. Symptoms should guide the extent of microbiologic evaluation and reflexive MTB PCR testing is not warranted if risk factors are absent. Disclosures All authors: No reported disclosures.

scholarly journals Risk Factors and Management of Osteoporosis Post-Transplant

Medicina ◽  
2020 ◽  
Vol 56 (6) ◽  
pp. 302
Author(s):  
Karthik Kovvuru ◽  
Swetha Rani Kanduri ◽  
Pradeep Vaitla ◽  
Rachana Marathi ◽  
Shiva Gosi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Diagnostic Tests ◽  
Negative Impact ◽  
Bone Biopsy ◽  
Solid Organ ◽  
Cell Transplant ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Parathyroid Dysfunction

Bone and mineral disorders are common after organ transplantation. Osteoporosis post transplantation is associated with increased morbidity and mortality. Pathogenesis of bone disorders in this particular sub set of the population is complicated by multiple co-existing factors like preexisting bone disease, Vitamin D deficiency and parathyroid dysfunction. Risk factors include post-transplant immobilization, steroid usage, diabetes mellitus, low body mass index, older age, female sex, smoking, alcohol consumption and a sedentary lifestyle. Immunosuppressive medications post-transplant have a negative impact on outcomes, and further aggravate osteoporotic risk. Management is complex and challenging due to the sub-optimal sensitivity and specificity of non-invasive diagnostic tests, and the underutilization of bone biopsy. In this review, we summarize the prevalence, pathophysiology, diagnostic tests and management of osteoporosis in solid organ and hematopoietic stem cell transplant recipients.

scholarly journals A Novel Secondary Neoplasm Following Allogeneic Hematopoietic Stem Cell Transplant: Mixed Donor-Recipient Primitive Mesenchymal Proliferation of the Liver

2021 ◽  
pp. 109352662110016
Author(s):  
Brian Earl ◽  
Zi Fan Yang ◽  
Harini Rao ◽  
Grace Cheng ◽  
Donna Wall ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Post Transplant

Post-hematopoietic stem cell transplant secondary solid neoplasms are uncommon and usually host-derived. We describe a 6-year-old female who developed a mixed donor-recipient origin mesenchymal stromal tumor-like lesion in the liver following an unrelated hematopoietic stem cell transplant complicated by severe graft-versus-host disease. This lesion arose early post-transplant in association with hepatic graft-versus-host disease. At 12 years post-transplant, the neoplasm has progressively shrunken in size and the patient remains well with no neoplasm-associated sequelae. This report characterizes a novel lesion of mixed origin post-transplant and offers unique insights into the contribution of bone marrow-derived cells to extra-medullary tissues.

Sign in / Sign up

Export Citation Format

Share Document