scholarly journals The Value of Tissue Polymerase Chain Reaction Testing for the Diagnosis of Tissue-Invasive Cytomegalovirus Disease Following Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3420-3420
Author(s):  
Armin Rashidi ◽  
Kiran R Vij ◽  
Richard S Buller ◽  
Kristine M Wylie ◽  
Gregory A Storch ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Predictive Value ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Double Negative ◽  
Double Positive ◽  
Allogeneic Hct ◽  
The Cost ◽  
Cmv Disease

Abstract Background: CMV disease is a major complication of allogeneic hematopoietic cell transplantation (HCT). Our widely used diagnostic modalities (H&E-based morphology and CMV IHC) are suboptimal in accuracy and frequently equivocal. Furthermore, current therapies for CMV disease are toxic and can cause serious complications such as prolonged neutropenia or progressive renal insufficiency. As a result, more accurate diagnosis that would help avoid potentially toxic treatments in patients who are truly negative for disease is highly desirable. The purpose of this study was to evaluate whether CMV PCR performed on formalin-fixed paraffin-embedded (FFPE) tissue offers additional diagnostic value to H&E/IHC in allogeneic HCT recipients. Methods: Following the approval by our institutional review board, the electronic medical records of all adult patients who underwent an allogeneic HCT at Washington University School of Medicine (St. Louis, MO) between 2010 and 2015 and had a post-transplant upper/lower endoscopy were retrospectively reviewed. An additional inclusion criterion was the availability of CMV DNA PCR on the blood within 7 days of biopsy.FFPE specimens were reviewed by a pathologist who was blinded to clinical and molecular results. The specimens were reviewed for H&E-based morphology and IHC findings. Tissue PCR was performed by a laboratory technician who was blinded to clinical, H&E, and IHC findings. Results: A total of 151 samples were included. Concurrent CMV viremia was present in 38% of cases. According to H&E/IHC results, cases were classified as double-positive (n = 17), double-negative (n = 105), or equivocal (n = 29) (Table 1). In receiver operating characteristic curve analysis for classification of H&E/IHC-concordant cases using tissue PCR, the optimal cycle threshold (Ct) value was 40 (area under the curve = 0.91, P < 0.001, sensitivity 94%, specificity 79%, positive predictive value 42%, and negative predictive value 99%; Figure 1). Using this cutoff, 45% of equivocal cases were classified as negative, suggesting that anti-CMV treatment in almost half of H&E/IHC-equivocal cases is unnecessary and potentially detrimental. Among viremic, H&E/IHC-concordant cases, tissue PCR with a cutoff Ct of 40 had a sensitivity of 100%, specificity of 50%, PPV of 44%, and NPV of 100%. Among non-viremic, H&E/IHC-concordant cases, these numbers were 80%, 91%, 36%, and 99%, respectively. In this analysis on viremic cases, all double-positive and 50% of double-negative cases were classified positive, while 31% of equivocal cases were classified negative. In non-viremic patients, 91% of double-negatives, 20% of double-positives, and 62% of equivocal cases were classified negative. Conclusions: Tissue PCR is a useful adjunct to H&E and IHC, particularly in H&E/IHC-equivocal cases, and can help avoid unnecessary, potentially toxic, anti-CMV treatment in cases without tissue-invasive disease. We propose the following algorithm: (i) If the cost and labor associated with tissue PCR on all patients are prohibitive, start with H&E and IHC. Perform tissue PCR in H&E/IHC-equivocal cases and consider this test also in non-viremic, H&E/IHC-positive cases. In all other cases forgo tissue PCR. (ii) If the cost and labor are not prohibitive, perform PCR on all cases. A negative PCR rules out CMV disease. In PCR-positive cases, use H&E/IHC results and treat only if H&E and IHC are both positive. One limitation of our study is related to using FFPE specimens rather than the real-life fresh tissue. Our results warrant testing in prospective studies. Disclosures DiPersio: Incyte Corporation: Research Funding.

High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation

2021 ◽  
pp. 107815522110604
Author(s):  
Kelly G Hawks ◽  
Amanda Fegley ◽  
Roy T Sabo ◽  
Catherine H Roberts ◽  
Amir A Toor
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Cmv Infection ◽  
Allogeneic Hct ◽  
Clinically Significant ◽  
Cmv Disease ◽  
Cmv Prophylaxis

Introduction Cytomegalovirus (CMV) is one of the most common and clinically significant viral infections following allogeneic hematopoietic cell transplantation (HCT). Currently available options for CMV prophylaxis and treatment present challenges related to side effects and cost. Methods In this retrospective medical record review, the incidence of clinically significant CMV infection (CMV disease or reactivation requiring preemptive treatment) following allogeneic HCT was compared in patients receiving valacyclovir 1 g three times daily versus acyclovir 400 mg every 12 h for viral prophylaxis. Results Forty-five patients who received valacyclovir were matched based on propensity scoring to 35 patients who received acyclovir. All patients received reduced-intensity conditioning regimens containing anti-thymocyte globulin. Clinically significant CMV infection by day + 180 was lower in the valacyclovir group compared to the acyclovir group (18% vs. 57%, p = 0.0004). Patients receiving valacyclovir prophylaxis also had less severe infection evidenced by a reduction in CMV disease, lower peak CMV titers, delayed CMV reactivation, and less secondary neutropenia. Conclusion Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted. Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.

scholarly journals Antiviral prophylaxis for cytomegalovirus infection in allogeneic hematopoietic cell transplantation

2018 ◽  
Vol 2 (16) ◽  
pp. 2159-2175 ◽  
Author(s):  
Kaiwen Chen ◽  
Matthew P. Cheng ◽  
Sarah P. Hammond ◽  
Hermann Einsele ◽  
Francisco M. Marty
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Preemptive Therapy ◽  
Antiviral Prophylaxis ◽  
Cmv Infection ◽  
Allogeneic Hct ◽  
All Cause Mortality ◽  
Cmv Disease

Abstract Patients treated with allogeneic hematopoietic cell transplantation (HCT) are at risk of cytomegalovirus (CMV) reactivation and disease, which results in increased morbidity and mortality. Although universal antiviral prophylaxis against CMV improves outcomes in solid organ transplant recipients, data have been conflicting regarding such prophylaxis in patients undergoing allogeneic HCT. We conducted a systematic review of randomized trials of prophylactic antivirals against CMV after allogeneic HCT to summarize the evolution of the field over the last 35 years and evaluate the prophylactic potential of antiviral agents against CMV after allogeneic HCT. Electronic databases were queried from database inception through 31 December 2017. For included studies, incidence of CMV infection and all-cause mortality were collected as primary outcomes; CMV disease incidence, use of preemptive therapy, and drug toxicities were collected as secondary outcomes. Nineteen clinical trials conducted between 1981 and 2017 involving a total of 4173 patients were included for review. Prophylactic strategies included use of acyclovir, valacyclovir, ganciclovir, maribavir, brincidofovir, and letermovir compared with placebo or a comparator antiviral. Fourteen trials that compared antiviral prophylaxis with placebo demonstrated overall effectiveness in reducing incidence of CMV infection (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.42-0.58), CMV disease (OR, 0.56; 95% CI, 0.40-0.80), and use of preemptive therapy (OR, 0.51; 95% CI, 0.42-0.62; 6 trials); however, none demonstrated reduction in all-cause mortality (OR, 0.96; 95% CI, 0.78-1.18) except the phase 3 trial of letermovir (week-24 OR, 0.59; 95% CI, 0.38-0.98). Additional research is warranted to determine patient groups most likely to benefit from antiviral prophylaxis and its optimal deployment after allogeneic HCT.

scholarly journals Erythropoietin therapy after allogeneic hematopoietic cell transplantation: a prospective, randomized trial

Blood ◽  
2014 ◽  
Vol 124 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Aurélie Jaspers ◽  
Frédéric Baron ◽  
Évelyne Willems ◽  
Laurence Seidel ◽  
Kaoutar Hafraoui ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Prospective Randomized Trial ◽  
Allogeneic Hct ◽  
Transfusion Requirements ◽  
Key Points

Key Points Erythropoietin therapy can be effective to hasten erythroid recovery and reduce transfusion requirements after allogeneic HCT.

The Effect of In Vivo T-Cell Depletion with Alemtuzumab on Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3014-3014
Author(s):  
Julio Delgado ◽  
Srinivas Pillai ◽  
Reuben Benjamin ◽  
Dolores Caballero ◽  
Rodrigo Martino ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Mixed Chimerism ◽  
Allogeneic Hct ◽  
Reduced Intensity

Abstract Reduced-intensity allogeneic hematopoietic cell transplantation (HCT) is increasingly considered as a therapeutic option for young patients with advanced chronic lymphocytic leukemia (CLL). We report 59 consecutive CLL patients who underwent allogeneic HCT following fludarabine and melphalan conditioning at four different institutions. For graft-versus-host disease (GVHD) prophylaxis, 38 patients (Cohort 1) received alemtuzumab (20–100 mg) and cyclosporine; and 21 patients (Cohort 2) received cyclosporine plus methotrexate or mycophenolate. Donors were 47 HLA-matched siblings and 12 unrelated volunteers, 6 of whom were mismatched. Median age at transplant was 53 (range, 34–64) years and median number of previous chemotherapy regimens was 3 (1–6), with 39% of patients being refractory to fludarabine. Nine patients had previously failed an autologous HCT. Fluorescent in-situ hybridization and IgVH mutation status data were available in 33 (56%) and 31 (53%) patients, respectively, being unfavorable (17p- or 11q-) in 22 (67%) and unmutated in 24 (77%) of them. All but 1 patient engrafted, and the median interval to neutrophil recovery (> 0.5 × 109/l) was 14 (range, 10–36) days. Twenty patients (34%), mostly from Cohort 1, received escalated donor lymphocyte infusions due to mixed chimerism or disease relapse. The overall complete response rate among 53 patients with measurable disease at the time of transplantation was 70%, whereas 21% had stable disease. Grade II-IV acute GVHD was observed in 14 (37%) and 12 (57%) patients from Cohorts 1 and 2, respectively (P = 0.17). Extensive chronic GVHD was observed in 3 (8%) and 10 (48%) patients from Cohorts 1 and 2, respectively (P < 0.01). The incidence of cytomegalovirus reactivation was not significantly different between cohorts (67% vs 47%, P = 0.23). With a median follow-up of 36 (range, 3–99) months for survivors, 18 (30%) patients have died, 3 of progressive disease and 15 of transplant-related complications. The 3-year overall survival (OS), progression-free survival (PFS) and non-relapse mortality were 66% (95% CI 48–84%), 38% (20–56%) and 21% (8–34%), respectively, for Cohort 1 and 65% (44–86%), 54% (32–76%) and 29% (10–48%) for Cohort 2 (P = 0.66; P = 0.33; and P = 0.53). Despite low patient numbers, alemtuzumab seemed particularly effective for unrelated donor recipients, with a 3-year OS and PFS of 54% and 40% for Cohort 1; and 33% and 0% for Cohort 2 (P = 0.02 and P = 0.07). In conclusion, results with reduced-intensity allogeneic HCT are promising for these poor-prognosis patients. Furthermore, the alemtuzumab-based regimen was effective in reducing the chronic GVHD rate with no negative effect on NRM, PFS or OS.

Association of HMGB1 Polymorphisms with Outcome After Allogeneic Hematopoietic Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2260-2260
Author(s):  
Brian Kornblit ◽  
Tania Nicole Masmas ◽  
Søren Lykke Petersen ◽  
Hans O Madsen ◽  
Carsten Heilmann ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Minor Allele ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Strong Linkage Disequilibrium ◽  
Myeloablative Conditioning ◽  
Allogeneic Hct ◽  
Related Mortality

Abstract Abstract 2260 Poster Board II-237 Several studies have demonstrated that genetic variation in cytokine genes can modulate the immune reactions after allogeneic hematopoietic cell transplantation (HCT). High mobility group box 1 protein (HMBG1) is a pleiotropic cytokine that functions as a proinflammatory signal, important for the activation of antigen presenting cells (APC) and propagation of inflammation. HMGB1 is implicated in the pathophysiology of a variety of inflammatory diseases, and we have recently found the variation in the HMGB1gene to be associated with mortality in patients with systemic inflammatory response syndrome (SIRS). To assess the impact of the genetic variation in HMGB1 on outcome after allogeneic HCT, we genotyped 276 and 146 patient/donor pairs treated with allogeneic HCT for hematologic malignancies following myeloablative or non-myeloablative conditioning. Associations between genotypes and outcome were only observed in the cohort treated with myeloablative conditioning. Patient homozygosity or heterozygosity for the –1377delA minor allele was associated with increased risk of relapse (hazard ratio (HR) 2.11, P=0.02) and increased relapse related mortality (RRM) (P=0.03). The –1377delA minor allele has previously been associated with mortality in patients with SIRS, and although SIRS and allogeneic HCT are different entities the confirmative association of this polymorphic locus with mortality in 2 independent studies suggests that it is of pathophysiological importance. The three polymorphisms, 3814C>G, 1177G>C and 2351insT, tended to have the same effect on transplantation outcome, due to a moderate to strong linkage disequilibrium between loci. Of these three polymorphisms, patient homozygosity for the 3814C>G minor allele showed the strongest association with increased overall survival (HR 0.13, P=0.04), progression free survival (HR 0.30, P=0.05) and decreased probability of RRM (P=0.03). Patient carriage of the 2351insT minor allele reduced the risk of grade 2 to 4 acute graft versus host disease (GVHD) (HR 0.60, P=0.01), while donor carriage of the minor allele displayed a gene dosage effect, with a successive increase in risk of developing limited or extensive chronic GVHD per minor allele carried (HR 1.54, P=0.01). That patient HMGB1 genotypes were associated with outcomes dependent on primarily patient APCs, and that donor genotypes were associated with a, in part, donor APC dependent outcome, could suggest that the polymorphisms in HMGB1 influence the transcription of HMGB1 in APCs induced by the proinflammatory milieu after myeloablative conditioning, rather than the passively released from damaged cells, although these two mechanisms are not mutually exclusive. Our findings suggest that the inherited variation in HMGB1 is associated with outcome after allogeneic HCT following myeloablative conditioning. None of the polymorphisms were associated with treatment related mortality. Disclosures: No relevant conflicts of interest to declare.

Comparison of 5-Azacytidine Versus Allogeneic Hematopoietic Cell Transplantation In Elderly (≥ 60 years) Patients with De Novo High-Risk MDS - a Retrospective Matched Pair Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3500-3500
Author(s):  
Uwe Platzbecker ◽  
Johannes Schetelig ◽  
Juergen Finke ◽  
Rudolf Trenschel ◽  
Bart Lee Scott ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
De Novo ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Disease Stage ◽  
Advisory Committees ◽  
Allogeneic Hct

Abstract Abstract 3500 Background: Myelodysplastic syndromes (MDS) are a disease of the elderly in whom until recently, allogeneic hematopoietic cell transplantation (HCT) has not been considered a reasonable therapeutic option. Best supportive care (BSC), only including transfusion support, has been the standard of care for the majority of these patients (pts). However, innovations in transplant protocols have changed that approach resulting in an increased frequency of allogeneic HCT. Further, several innovative non-transplant therapeutic modalities for MDS pts have been developed. In fact, treatment with DNA-methyltransferase inhibitors (MTI) such as 5-azacytidine (5-aza) has changed the natural course of the disease and prolonged median survival by an average of 9 months compared to BSC. However, allogeneic HCT is currently still the only modality with proven curative potential, although there has been no true randomized trial comparison of HCT to 5-aza therapy only. Methods: Consequently, we performed a retrospective analysis in 126 pts, 60 –77, (median 64) years of age with de novo high-risk MDS according to FAB classification (RAEB n=88, RAEB-t n=20, CMML n=18) undergoing allogeneic HCT at a median of 9 months from initial MDS diagnosis. Cytogenetics were available in 108 pts (good: n=63, intermediate: n=18, poor: n=27), resulting in IPSS classification (in 107 pts) of INT-1 (n=28), INT-2 (n=45) or HIGH (n=34). The ECOG was available in 125 pts, and was either 0 (19%), 1 (66%) or >1 (15%). Prior to HCT, most pts had progressed to a higher stage than present at diagnosis (RAEB n=45, RAEB-t n=10, CMML n=10, AML n=61), the median blast count in the marrow being 12%. Patients were prepared for HCT with one of several reduced (RIC, n=78) or more conventional intensity (n=48) conditioning regimens followed by stem cells from either related (n=50) or unrelated (n=76) donors. The outcome of this high-risk MDS cohort was compared to patients from the French (GFM) 5-aza patient registry matched for age, gender, prior induction chemotherapy, time from diagnosis to therapy (either HCT or 5-aza), disease stage and cytogenetics at diagnosis as well as at start of therapy. The groups could be well matched except for age (median age 5-aza: 67 vs. HCT: 64; p=0.001). Further, the HCT group included more pts with a higher ECOG score (ECOG>0: 81% vs. 59%; p=0.05) prior to start of therapy. Results: With a median follow-up of 20 months for surviving pts from the start of therapy the estimated 3-year overall survival (OS) was 39% (95% CI, 30% to 48%) for HCT and 7% (95% CI, 0 to 16%) for 5-aza, respectively. In multivariate Cox regression analysis, ECOG score (p<0.001), disease stage p=0.021), cytogenetic risk group (p=0.002) and type of treatment (5-aza vs. HCT HR: 1.8; p=0.003) were associated with survival. Conclusion: These retrospective data suggest that allogeneic HCT from related or unrelated donors, using various conditioning approaches, might offer a meaningful survival benefit compared to 5-aza in patients with high-risk MDS, even in the 7th decade of life. There is a need for prospective clinical trials in order to determine the place of this approach within the growing therapeutic opportunities for pts with MDS. Disclosures: Platzbecker: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ades:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Infusion of donor-derived CD8+ memory T cells for relapse following allogeneic hematopoietic cell transplantation

2018 ◽  
Vol 2 (6) ◽  
pp. 681-690 ◽  
Author(s):  
Lori Muffly ◽  
Kevin Sheehan ◽  
Randall Armstrong ◽  
Kent Jensen ◽  
Keri Tate ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Memory T Cells ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Allogeneic Hct ◽  
Key Points ◽  
Cd8 Memory T Cells

Key Points Phenotypic TM isolation from unmanipulated donor apheresis via CD45RA depletion followed by CD8+ enrichment is feasible. TM infusion for patients with relapse after allogeneic HCT was safe and resulted in minimal GVHD.

scholarly journals Long-Term Survival and Late Deaths After Allogeneic Hematopoietic Cell Transplantation

2011 ◽  
Vol 29 (16) ◽  
pp. 2230-2239 ◽  
Author(s):  
John R. Wingard ◽  
Navneet S. Majhail ◽  
Ruta Brazauskas ◽  
Zhiwei Wang ◽  
Kathleen A. Sobocinski ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Older Age ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Term Survival ◽  
Long Term Survival ◽  
Allogeneic Hct

PurposeAllogeneic hematopoietic cell transplantation (HCT) is curative but is associated with life-threatening complications. Most deaths occur within the first 2 years after transplantation. In this report, we examine long-term survival in 2-year survivors in the largest cohort ever studied.Patients and MethodsRecords of 10,632 patients worldwide reported to the Center for International Blood and Marrow Transplant Research who were alive and disease free 2 years after receiving a myeloablative allogeneic HCT before 2004 for acute myelogenous or lymphoblastic leukemia, myelodysplastic syndrome, lymphoma, or severe aplastic anemia were reviewed.ResultsMedian follow-up was 9 years, and 3,788 patients had been observed for 10 or more years. The probability of being alive 10 years after HCT was 85%. The chief risk factors for late death included older age and chronic graft-versus-host disease (GVHD). For patients who underwent transplantation for malignancy, relapse was the most common cause of death. The greatest risk factor for late relapse was advanced disease at transplantation. Principal risk factors for nonrelapse deaths were older age and GVHD. When compared with age, sex, and nationality-matched general population, late deaths remained higher than expected for each disease, with the possible exception of lymphoma, although the relative risk generally receded over time.ConclusionThe prospect for long-term survival is excellent for 2-year survivors of allogeneic HCT. However, life expectancy remains lower than expected. Performance of HCT earlier in the course of disease, control of GVHD, enhancement of immune reconstitution, less toxic regimens, and prevention and early treatment of late complications are needed.

Frequent genomic alterations in epithelium measured by microsatellite instability following allogeneic hematopoietic cell transplantation in humans

Blood ◽  
2006 ◽  
Vol 107 (8) ◽  
pp. 3389-3396 ◽  
Author(s):  
Philipp Faber ◽  
Paul Fisch ◽  
Miguel Waterhouse ◽  
Annette Schmitt-Gräff ◽  
Hartmut Bertz ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Genomic Alterations ◽  
Graft Versus Host ◽  
Allogeneic Hct ◽  
Colonic Crypts ◽  
Autologous Hct

Abstract Although typically found in cancers, frameshift mutations in microsatellites have also been detected in chronically inflamed tissues. Allogeneic hematopoietic cell transplantation (HCT) may potentially produce chronic tissue stress through graft-versus-host reactions. We examined non-neoplastic epithelial tissues (colon, buccal) obtained 1 to 5061 days after human allogeneic HCT for the presence of genomic alterations at 3 tetranucleotide and 3 mononucleotide microsatellite loci. Novel bands indicative of microsatellite instability (MSI) at tetranucleotide repeats were detected in laser-microdissected colonic crypts and in buccal smears of 75% and 42% of patients who received an allograft, respectively. In contrast, no MSI was found in similar tissues from control subjects and from patients after intensive chemotherapy or in buccal cells from patients after autologous HCT. The MSI found in colon, which was often affected by graft-versus-host disease, was not due to loss of expression or nitrosylation of DNA repair proteins. MSI in clinically intact oral mucosa was more frequently found at later time points after HCT. MSI was also found in 3 posttransplant squamous cell cancers examined. Our data show that genomic alterations in epithelium regularly occur after allogeneic HCT and may be implicated in the evolution of posttransplantation diseases, including secondary cancer.

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