Outcomes of Cytomegalovirus Monitoring in Autologous Transplantation: A Single Institution Experience

Abstract Introduction: Identification of patients seropositive for cytomegalovirus (CMV) prior to stem cell transplant (SCT) is a well-accepted practice across institutions designed to reduce a known cause of morbidity and mortality in this population, but the role of monitoring and preemptive approaches to CMV identification and treatment are controversial and not standardized in autologous transplantation. The preemptive approach necessitates the use of significant resources and requires persistent patient involvement. Patients undergoing autologous SCT are at a relatively low risk for CMV reactivation, especially those seronegative for CMV at the time of transplant. Here, we show that the necessity of routine monitoring of autologous transplant patients is of minimal clinical value. Methods: To determine the efficacy of the CMV monitoring protocol currently in place at our institution in detecting patients who would later develop CMV reactivation and disease following autologous SCT, we retrospectively analyzed the charts of 218 adult patients between 11/1/14 and 8/1/19 who underwent transplant at St. Louis University Hospital. No patients underwent CD34 selected stem cell infusions. The protocol stipulated the following: CMV IgG/IgM and CMV DNA PCR prior to preparative regimen followed by weekly CMV DNA PCR to day +30 . We correlated the predictive ability of positive results on any of these screening tests to identify whether patients would later develop quantifiable CMV DNA PCR positivity, clinical manifestations of CMV disease, and/or require pharmacologic treatment for CMV. Results: Quantifiable pre-BMT DNA PCR was positive in only 0.46% of patients, and 97.79% of patients were DNA PCR negative prior to transplant. CMV IgG was positive in 56.4% patients, and only 22.1% of patients in this group went on to develop a quantifiable post-transplant PCR. Of the remaining 43.6% of patients initially testing negative for CMV IgG, no patients went on to develop a quantifiably positive post-transplant PCR. Regardless of seropositivity, only 0.08% of the 1,191 PCRs performed during the study period were found to be quantifiable. Further, no patients in our cohort developed CMV disease or required CMV treatment during the monitoring period. This trend persisted despite stratification by age, diagnosis, transplant number, and preparative regimen. Conclusion: When clinically-significant CMV is defined by cases requiring treatment or the development of end-organ disease, no screening tests performed elicited clinical action. Laboratory-based CMV surveillance, based on our data, has minimal diagnostic implications and represents an overly-stringent practice in a set of patients already utilizing a substantial share of healthcare resources. We believe that pre-transplant screening for CMV IgM serology and CMV DNA PCR can be safely eliminated in the autologous SCT population at our institution while CMV IgG still plays a role in determining candidacy for CMV-negative blood products. We also propose the elimination of serial post-transplant monitoring with DNA PCR in patients without clinical signs, symptoms, or pathologic findings suggestive of CMV disease. We have changed the protocol to test for CMV PCR only if there are clinical scenarios that indicate a utility, such as prolonged fever post-transplant, unexplained cytopenias, or unexplained pneumonitis, colitis, or hepatitis. By extension, other centers should consider determining the necessity of CMV screening in their autologous transplant population given the potential resource conservation and reduction in healthcare expenditures. Disclosures Fesler: abbvie: Consultancy, Speakers Bureau; incyte: Consultancy, Speakers Bureau; sanofi: Speakers Bureau; morphosys: Speakers Bureau; epizyme: Consultancy; jazz: Consultancy; Skipta: Consultancy; Best Doctors: Consultancy; Aptitude Health: Consultancy; Care Dx: Consultancy; Opinionsite: Consultancy. Goldenberg: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

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CMV reactivation in allogeneic hematopoietic stem cell transplant patients receiving post-transplant cyclophosphamide.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e18533 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e18533-e18533

Author(s):

Paul Markowski ◽

Dale G. Schaar ◽

Catherine Wei ◽

Anne Tyno

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Published Data ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Post Transplant ◽

Transplant Patients ◽

Number Of Patients ◽

Cmv Reactivation

e18533 Background: Post transplant cyclophosphamide (PTCY) has been shown to be an effective treatment for prevention of graft versus host disease (GVHD). However, this increased immune suppression rates may increase the risk of CMV reactivation. There is limited published data addressing CMV reactivation in this patient population. Additionally there is no data on the efficacy of prophylactic letermovir in the patients who have received PTCY. In this study we analyzed the incidence of CMV reactivation in patients treated with PTCY and those not treated with PTCY, as well as the efficacy of letermovir in preventing CMV reactivation in the PTCY population. Methods: We conducted a retrospective review of MUD, MRD, and haploidentical stem cell transplant patients at our institution from 1/1/2014 until 12/10/2018. We analyzed the incidence of CMV reactivation (PCR > 137 DNA IU/ml), peak of CMV PCR titer and time to reactivation within the first 100 days post-transplant. Results: There were 150 patients with at least 60 days of follow-up that were included in this study. These patients were split into three groups: No post-transplant cyclophosphamide (NPTCY) (N = 64), received post-transplant cyclophosphamide (PTCY) (N = 70), and received PTCY and letermovir prophylaxis. (L-PTCY) (N = 15). The incidence of CMV reactivation was increased in the PTCY patients when compared to the NPTCY (44% vs 29%). In the NPTCY patients the donor (D) serostatus increased the risk of CMV reactivation (Recipient (R)+ D+ 73% vs R+D-36%) conversely in the PTCY group the donor CMV status did not influence reactivation rates (R+D+ 52% vs R+D- 81%). The CMV reactivation rate in the L-PTCY patients was lower when compared to the PTCY patients (21% vs 44%), additionally the L-PTCY patients had much lower peak CMV titers compared to PTCY group (445 vs 2112 IU/ml). Conclusions: This study demonstrates that there is an increased incidence of CMV reactivation in patients who receive PTCY. Additionally, the donor CMV serostatus does not appear to influence the incidence of CMV reactivation in patients receiving post-transplant CY. Although the number of patients in the L-PTCY group is small, it does appear to be an effective prophylactic treatment in patients receiving PTCY.

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Cytomegalovirus Management in Adult Hematopoietic Stem Cell Transplant Patients with Pre-Engraftment Viremia: A Single-Center, Retrospective, Descriptive Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.863 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S357-S357

Author(s):

Isabella Martin ◽

Robin Avery ◽

Douglas Gladstone ◽

Richard Ambinder ◽

Noah Tucker ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Conditioning Regimen ◽

Bone Marrow Toxicity ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Post Transplant ◽

Cmv Disease

Abstract Background Scant data exist regarding cytomegalovirus (CMV) viremia in hematopoietic stem cell transplant (HSCT) recipients during the pre-engraftment period. The goal of this study was to describe management of CMV in neutropenic adult HSCT patients at our institution, and to assess the possible impact of different quantitative CMV PCR tests (QPCRs). Methods Post-HSCT monitoring at this center includes weekly CMV QPCR from plasma. Three different QPCR assays were used sequentially during the study period (1/2010–12/2015): two with lower limits of quantification (LLOQ) of 300 and 100 copies/mL through 4/2013, and after that the FDA-approved assay with LLOQ of 137 IU/mL. Medical records of first-time HSCT patients were reviewed. Pre-/peri-engraftment CMV was defined as detectable CMV DNA with [ANC] < 1000 cells/mm3. Information collected included demographics, donor/recipient CMV serostatus, conditioning regimen, CMV QPCR and ANC results, dates of CMV treatment, CMV disease within 100 days, and death within 6 months of HSCT. Data were analyzed with STATA v14. Results Of 1151 total HSCT, 76 patients had a positive CMV QPCR when ANC < 1000 cells/mm3. CMV was first detected a median of 12 days (0–48) post-transplant, and was above LLOQ at a median of 28 days (0–49). 71/76 (93%) were treated at a median of 33 days post-transplant (range 4–105 days), most with valganciclovir (40) or ganciclovir (30); 1 received foscarnet initially. 5 patients with low-level viremia were monitored without treatment. At initiation of therapy, median CMV level was 1471 (range 159–22,900) copies or IU/mL and ANC was 1202 (range 28–9680) cells/mm3. Median treatment duration was 34 days (range 9–392). Only 2 patients had possible tissue-invasive CMV disease. Conclusion Ganciclovir and valganciclovir were used to treat most pre- and peri-engraftment CMV viremia, despite potential bone marrow toxicity. The LLOQ of different CMV QPCR tests did not affect the viral threshold for starting treatment. The time between first CMV DNA detection (median day +12) and initiation of treatment (median day +33) suggests clinicians waited for CMV DNA and/or ANC to rise before treating. With this deferred-treatment approach, the proportion of patients with tissue-invasive disease remained low. Disclosures All authors: No reported disclosures.

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Cytomegalovirus reactivation following hematopoietic stem cell transplantation

The Journal of Infection in Developing Countries ◽

10.3855/jidc.2947 ◽

2013 ◽

Vol 7 (12) ◽

pp. 1003-1007 ◽

Cited By ~ 3

Author(s):

Sanjeev Kumar Sharma ◽

Suman Kumar ◽

Narendra Agrawal ◽

Lavleen Singh ◽

Anjan Mukherjee ◽

...

Keyword(s):

Developing Countries ◽

Stem Cell ◽

Gastrointestinal Tract ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Cell Transplant ◽

Post Transplantation ◽

Hematopoietic Stem ◽

Cmv Disease ◽

Cmv Reactivation

Introduction: There is a high prevalence of cytomegalovirus (CMV) seropositivity in developing countries. An apparent risk of CMV reactivation increases following hematopoeitic stem cell transplantation. With effective surveillance and timely treatment using anti-viral therapy, morbidity and mortality associated with CMV reactivation can be reduced. Objectives: To evaluate the incidence and morbidity associated with CMV reactivation following hematopoeitic stem cell transplantation. Methodology: We retrospectively analysed 136 hematopoeitic stem cell transplant recipients at our centre for CMV reactivation and their complications. Quantification of CMV-DNA was done by PCR. CMV disease was confirmed histologically via CMV inclusion bodies or immunostaining of biopsy of the affected organ, mainly the gastrointestinal tract. Results: A total of 13 out of 136 patients (9.56%) had CMV reactivation. 6 out of 13 patients had CMV disease, 3 of which died (23.1% of patients with CMV reactivation). CMV reactivation occurred at a median duration of 52.5 days post transplantation (range 35-178 days). The gastrointestinal tract was the organ most commonly affected by CMV. The median follow-up was 14 months (range 6 - 64 months). Conclusion: Through a higher rate of sero-prevalance in developing countries, the incidence of CMV infection following hematopoeitic stem cell transplantation is comparable to that reported in Western literature. Oral valganciclovir was an effective pre-emptive therapy for CMV disease.

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Impact of Pre-Engraftment Cytomegalovirus Viraemia in Allogeneic Haematopoetic Stem Cell Transplant Recipients

Blood ◽

10.1182/blood-2019-122368 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5656-5656

Author(s):

Joanne L C Tan ◽

Shio Yen Tio ◽

Michelle K Yong ◽

David Ritchie

Keyword(s):

Research Funding ◽

Cell Transplant ◽

Royal Melbourne Hospital ◽

Exact Test ◽

Post Transplant ◽

Cytomegalovirus Reactivation ◽

Increased Risk ◽

Cmv Disease ◽

Cmv Reactivation ◽

Neutrophil Engraftment

Background Cytomegalovirus (CMV) reactivation post- allogeneic transplant increases mortality(1). Very few studies have explored the significance of pre-engraftment CMV reactivation on subsequent CMV-related outcomes or therapy. Aim To determine the incidence and outcome of pre-engraftment CMV reactivation. Methods All consecutive patients transplanted May 2015-Jan 2019 at the Royal Melbourne Hospital were included in this observational retrospective study. Plasma CMV DNA load was monitored by real-time PCR assays twice per week. Pre-emptive CMV treatment was commenced when the CMV viral load was greater than 400 IU/ml. Risk factors for pre-engraftment CMV were assessed by univariate logistic regression analysis. The Mann-Whitney U test was used to compare post-transplant CMV reactivation and time of treatment initiation; the Fisher's exact test was used for CMV disease and acute graft versus host disease (aGVHD); neutrophil engraftment, relapse free survival (RFS) and overall survival (OS) were compared using the Log-Rank Method. Results Of the 220 patients, 182 patients had CMV reactivation and pre-engraftment CMV levels available. Of these 182, 102 (56%) had CMV detected on at least one occasion before engraftment (D-10 to D+30). No pre-transplant factors including conditioning type and CMV serostatus were found to be associated with the development of pre-engraftment CMV reactivation. Patients who had pre-engraftment viraemia patients had a shorter time to post-transplant CMV detection (p<0.0001; Y=27.2d vs N=36.3d). These patients also had a longer time to neutrophil engraftment (p=0.049, median 19d vs 18d). Despite the shorter time to detection, there was no difference in likelihood of commencement of pre-emptive anti CMV therapy (p=0.88), day of CMV therapy commencement (p=0.29) and the total length of treatment (p=0.82). Patients with pre-engraftment viraemia were not at an increased risk of CMV disease (P=0.65) or aGVHD (p=0.87). There was no difference in RFS (p=0.99) or OS (p=0.14). Conclusion These results suggest that pre-transplant CMV detection should not affect the decision to proceed to transplant or require earlier initiation of prophylactic or pre-emptive therapy. References Teira, P., Battiwalla, M., Ramanathan, M., Barrett, A. J., Ahn, K. W., Chen, M., Green, J. S., Saad, A., Antin, J. H., Savani, B. N., Lazarus, H. M., Seftel, M., Saber, W., Marks, D., Aljurf, M., Norkin, M., Wingard, J. R., Lindemans, C. A., Boeckh, M., Riches, M. L., & Auletta, J. J. (2016). Early cytomegalovirus reactivation remains associated with increased transplant-related mortality in the current era: a CIBMTR analysis. Blood, 127(20), 2427-2438. Accessed June 01, 2019. https://doi.org/10.1182/blood-2015-11-679639. Disclosures Yong: Merck Ltd: Honoraria. Ritchie:Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; BMS: Research Funding; Takeda: Research Funding; Beigene: Research Funding; Imago: Research Funding; Novartis: Honoraria; Sanofi: Honoraria.

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A Step Forward Towards Cytomegalovirus Free Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood-2018-99-117068 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5708-5708

Author(s):

Alfaraj Abeer ◽

Daniel R Reed ◽

Gina Petroni ◽

Sandra Monson ◽

Paige Williams ◽

...

Keyword(s):

Stem Cell ◽

Viral Load ◽

Hematopoietic Stem Cell Transplantation ◽

Median Time ◽

Preemptive Therapy ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

Post Transplant ◽

Cmv Disease ◽

Cmv Reactivation

Abstract Introduction: Cytomegalovirus (CMV) reactivation remains one of the most serious complications after allogeneic hematopoietic stem cell transplantation (HSCT) occurring in up to 30-50% of HSCT recipients. CMV reactivation can lead to adverse outcomes including end-organ damage and graft failure. Prevention of CMV infection may improve outcomes of HSCT recipients; however, CMV reactivation can still occur in HSCT recipients despite receiving prophylactic acyclovir. In this study, we used prophylactic ganciclovir pre-transplant to reduce the incidence of CMV reactivation and CMV disease. Methods: To reduce the incidence of CMV reactivation and disease, ganciclovir was administered before transplantation (5 mg/kg twice daily intravenously from day −8 to day −2) for all donor and recipient seropositive allogeneic HSCT. This was followed by high dose valacyclovir or acyclovir starting day 0 until one year post-transplant. Patients were monitored weekly with serum CMV PCR through Day 100 post transplantation. Preemptive therapy was started for an elevated CMV viral load. CMV reactivation was defined as a CMV viral load of more than 135 IU/ml. Over the course of the analysis period, two different PCR methods were used for CMV viral load; since 2015 Roche Cobas AmpliPrep/Cobas TaqMan CMV test was implicated. CMV disease was defined as detection of CMV by one of the following diagnostic tests including: culture, immunohistochemistry staining, or histopathology examination accompanied by documentation of disease signs and symptoms of the affected organ. Statistical analysis was performed using SAS version 9.4. Logistic regression models were explored to assess the association of age, graft source, and disease type on CMV reactivation. We performed a retrospective analysis of all recipient or donor CMV seropositive patients who received their first allogeneic HSCT at the University of Virginia between 2012 and 2017. Results: Seventy-nine consecutive patients were treated. The median age was 58 years (range 20 to 72). The most common diagnoses were acute myeloid leukemia (n=39, 49%) and acute lymphocytic leukemia (n=11, 14% ). Graft sources were matched related donor, (n=24, 30%), matched unrelated donor, (n=28, 35%), haploidentical (n=4, 5%) and cord blood (n=23, 29%). 43 patients (55%) received myeloablative (CyTBI, BuCy and FluBu) conditioning. 36 patients (45%) received reduced intensity/nonmyeloablative conditioning (Flu/Cy/TBI+/- ATG, Flu/Cy/ATG ,Flu Mel, Flu Bu and Cy ATG). All patients received calcineurin inhibitor based prophylactic immunosuppressive therapy for GVHD prevention. 24 patients (30%) had CMV reactivation with median time of reactivation of 47 days post-transplant (range 27 to 229). 22 out of the 24 (88%) patients required treatment for CMV reactivation with a median treatment duration of 37 days (range 14 to 315). Patients were treated with either ganciclovir or foscarnet, as clinically indicated. The cumulative incidence of CMV reactivation at day 100 post-transplant was 27% with a 95% CI (18%-37%). The median highest viral load was 2130 copies/ml (range 151 to 3,250,000 copies/ml). There were no patients with biopsy proven CMV disease. There were no deaths attributed to CMV reactivation or disease. The median time-to neutrophil recovery (ANC > 500 k/uL) was 18 days and the median time to platelet count greater than 20,000 k/ul unsupported was 19 days. The incidence of acute GVHD (Grades II-IV) was 25 %. The incidence of significant acute kidney injury defined by serum creatinine of more than 2.5 mg/dL was 2.4 %. 1 year overall survival estimate was 54% with 95% CI (42-65%). In multivariate analysis, patients who received cord blood transplants, were approximately 4 times more likely to have a CMV reactivation (Odds Ratio 3.9 with a 95% CI(1.4-10.9)), p= 0.01, than those who did not. Conclusions:The incidence of CMV reactivation by day 100 of 27% with pre-transplant ganciclovir may be improved compared to historical controls of 30-50%.The use of pre-transplant ganciclovir was associated with no CMV disease, in this single center study.The use of pre-transplant ganciclovir is safe, with low incidence of kidney damage. These data suggest that pre-transplant ganciclovir with Preemptive therapy for viral reactivation should be considered regardless of graft source. Future prospective randomized trials are needed to evaluate strategies for CMV prophylactic regimens. Disclosures No relevant conflicts of interest to declare.

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Analysis of Factors Influencing Skin Toxicity after Autologous Hematopoeitic Stem Cell Transplant.

Blood ◽

10.1182/blood.v110.11.2882.2882 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2882-2882

Author(s):

Anuj Mahindra ◽

Brian Bolwell ◽

Ronald Sobecks ◽

Lisa Rybicki ◽

Stacey Brown ◽

...

Keyword(s):

Stem Cell ◽

Statistical Significance ◽

Autologous Transplantation ◽

Multivariable Analysis ◽

Significant Risk ◽

Skin Toxicity ◽

Significant Risk Factor ◽

Cell Transplant ◽

Increased Risk ◽

Preparative Regimen

Abstract Skin toxicity is a known but understudied complication of autologous stem cell transplantation (ASCT). Its assessment is complicated by the development of graft-vs-host disease following allogeneic transplantation. We chose therefore to study skin toxicity following autologous transplantation. We retrospectively reviewed the records of 392 patients undergoing ASCT to analyze risk factors for skin toxicity, its association with mucositis and its effect on survival. Skin toxicity was assessed three times a week during the transplant admission and was classified as none, mild, moderate, severe or life threatening. The most severe skin toxicity is used in this analysis. Mucositis was assessed using the modified oral mucositis assessment scale (OMAS). Median patient age was 53 years; 63% of patients had non-Hodgkin s lymphoma (NHL), 17.6% multiple myeloma, 13.5% Hodgkin disease (HD) and 5.9% acute leukemia. Peripheral blood progenitor cells were mobilized with G-CSF alone (36%) or the combination of etoposide plus G-CSF (64%). The preparative regimen was busulfan (Bu)/cyclophosphamide (Cy) /etoposide in 82% and Bu/Cy alone in 18%. Two hundred and sixty patients (67%) developed skin toxicity of which 143 patients (36.5%) had mild, 105 (26.8%) had moderate and 16 (3.9%) had severe skin toxicity. Factors associated with the development of any skin toxicity in univariable analysis were male gender (p=0.028), diagnosis of NHL (p<0.001) or HD (p=0.001), higher number of prior chemotherapy regimens (p<0.001), mobilization regimen containing etoposide (p< 0.001) and ASCT preparative regimen containing etoposide (p<0.001). Moderate skin toxicity correlated with the above as well. Only the inclusion of etoposide in the mobilization regimen was associated with an increased risk of severe skin toxicity (p=0.035). Etoposide in the preparative regimen remained the most significant risk factor for the development of skin toxicity in multivariable analysis. Higher OMAS score was associated with increased severity of skin toxicity (p<0.001) as shown in the boxplot below: Patients with severe skin toxicity appeared to have worse overall survival (p=0.054) and relapse-free survival (p=0.08), but these findings did not reach statistical significance. Conclusion: A substantial proportion of patients develop skin toxicity following autotransplantation. The inclusion of etoposide in the preparative regimen is associated with a significant increased frequency in multivariable analysis. The severity of skin toxicity correlates closely with the severity of mucositis. Figure Figure

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Oral Valganciclovir As Preemptive Therapy for Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Blood ◽

10.1182/blood.v124.21.5855.5855 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5855-5855 ◽

Cited By ~ 1

Author(s):

Vildan Ozkocaman ◽

Fahir Ozkalemkas ◽

Ridvan Ali ◽

Yasemin Karacan ◽

Tuba Ersal ◽

...

Keyword(s):

Stem Cell ◽

Viral Load ◽

Myeloid Leukemia ◽

Preemptive Therapy ◽

Cell Transplant ◽

Cmv Infection ◽

Intravenous Ganciclovir ◽

Hematopoietic Stem ◽

Cmv Disease ◽

Cmv Reactivation

Abstract Introduction: Cytomegalovirus (CMV) infection remains one of the most important complications after allogeneic hematopoietic stem cell transplantation (AlloHSCT). Preemptive therapy with oral VGC or intravenous ganciclovir has replaced universal prophylaxis. We investigated the effect of oral VGC as preemptive therapy on CMV reactivation or infection in AlloHSCT. Patient & Methods: We retrospectively studied 30 consecutive adult recipients of HLA-identical sibling allogeneic peripheral blood stem cell transplant from June 2011 through June 2014 to analyze the safety and efficacy of preemptive therapy for the treatment of CMV infection. Among 30 patients we studied the results of 13 patients with CMV DNA positivity. All 13 recipients and their donors were seropositive for CMV Ig G status. Their diagnosis of pretransplantation were as 8 acute myeloid leukemia (61 %) and 5 acute lymphocytic leukemia (39 %). Median age was 39 years (range 21-54). There were 9 men and 4 women (Table-1). The patients received no prophylaxis against CMV. Blood/serum samples from all patients were routinely monitored for CMV-DNA using PCR twice weekly. We iniciated pre-emptive therapy for CMV as the viral load was above and equal to 500 copies/ml in two consecutive samples. VGC was given twice daily 900 mg for 2 weeks, and maintened at a dose daily 900 mg until viral load is undetectable. Results: The PCR test was persistently negative in 17 patients (57 %) and positive at least once in 13 (43%)patients. All patients with CMV reactivations were on immunsupressive treatment. CMV infection was cleared in most patients within 2 weeks, but for those with stable or increasing CMV levels, the induction period was continued. Twelve patients were treated with oral VGC on an outpatient basis and they all became CMV negative after the first week of treatment. Only one patient received intravenous ganciclovir and he was also CMV negative after the first week of treatment. While no positivity was identified in any of the patients who received VGC on day 21, clinically unimportant low titer CMV positivity was noted in three of these patients. VGC was continued at same dose and no positivity was detected after 2-3 weeks. We were obligated interrupt VGC in only four patients for serious side effects namely neutropenia and thrombocytopenia. We did not observe CMV-related mortality. Conclusions: We concluded that VGC therapy could be safely used at outpatient clinics, with frequent monitorization to prevent severe myelotoxicity. In conclusion, based on our findings, oral VGC is effective and safe in the pre-emptive treatment of CMV disease following allo-HSCT. Therefore, preemptive strategy by oral VGC appears preferable to the prevention of CMV disease in alloHSCT with its advantage of effectiveness and usage in outpatient clinic condition. Table- 1: Management and outcome of the patient characteristics with CMV-reactivation Patients with CMV reactivation/Total number of patient 13/30 Median age, years (range) 39 (21-54) Gender Male Female 9 4 Diagnosis AML ALL 8 5 CMV serologic status Donor+/Recipient + 13 Preperative regimen Bu-Cy CY-TBI Flu/Amsc(FLAMSA) 8 4 1 GVHD propylaxis CSA+MTX CSA+MTX+MM 12 1 GVHD prior to CMV reactivation Acute chronic without GVHD 7 1 5 Prednisolone treatment at the time of starting VCG Yes No 8 5 IST at the time of starting VGC Yes No 13 0 Median duration of CMV reactivation (day) 44 (8-330) Viral load before antivial treament (copies/ml) 1153 (78-12800) Treatment VGC (900 mg, twice daily for induction) GC (5 mg/kg, twice daily for induction) VGC+GC 9 (70 %) 1 (7 %) 3 (23 %) Total treatment duration (day) 24 (10-51) CMV DNA at the end of the treatment Conversion to negative Persistently positive (low titer < 50 copies/ml) 10 (77 %) 3 (23 %) Serious side effects Interruption of therapy due to neutropenia Interruption of therapy due to thrombocytopenia Reactivation 3 (23 %) 1 (7 %) 2 (15 %) Abbreviations: AML: acute myeloid leukemia, ALL: acute lymphoblastic leukemia, CMV: cytomegalovirus,GVHD: graft-versus host disease, CSA: cylosporine, MTX: methotrexate, MMF: mycophenolate mofetil, PDN:prednizolone, IST: Immunosupressive treatment, VGC: valganciclovir, GC: ganciclovir, Bu: Busulfan, Cy: cylophosphamide, TBI: total body irradiation Disclosures No relevant conflicts of interest to declare.

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Mucositis during Allogeneic Transplantation Determines Post-Transplant Serum Cyclosporin Levels

Blood ◽

10.1182/blood-2019-122363 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5662-5662

Author(s):

Joanne L C Tan ◽

Eric Wong ◽

Ashish Bajel ◽

Radha Ramanan ◽

Andrew B M Lim ◽

...

Keyword(s):

Stem Cell ◽

Renal Impairment ◽

Research Funding ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Prospective Evaluation ◽

Post Transplant ◽

Oral Cyclosporin ◽

Significant Difference ◽

Cmv Reactivation

Introduction Intestinal mucosal injury is a common complication following allogeneic stem cell transplant (alloHSCT), especially with myeloablative and TBI-based (total body irradiation) conditioning regimens1. Prospective evaluation studies have shown that intestinal malabsorption persists for several weeks following conditioning, beyond visible resolution of mucositis and bowel integrity2. Serum cyclosporin levels in the post-transplant period (when patients are taking oral cyclosporin) may be affected by reduced gut absorption and could influence early transplant related outcomes. Aim To determine the relationship between mucositis severity, cyclosporin levels, and post-transplant outcomes. Methods 169 patients who received myeloablative (BuCy, CyTBI, EtoTBI) or reduced-intensity (FluMel) allo-HSCT at the Royal Melbourne Hospital were studied. Serum cyclosporin levels were measured at 2 hours post oral dosing. Days of post-transplant total parental nutrition (TPN) were used as a surrogate for severity of gastrointestinal mucositis. To determine degree of renal impairment, creatinine values were recorded at baseline, D+30, D+60 and D+100. The incidence and severity of acute graft-versus-host disease (aGVHD) was recorded before D+100. The incidence of CMV viraemia before D+100 was recorded and analysed according to serum viral load. Patients with disease relapse (<6m versus >6m) were compared with patients without. Results Linear regression analysis showed an inverse correlation between days requiring TPN with the post SCT 100-day median cyclosporin level (p<0.0001, R2=0.23). Higher median cyclosporin level was associated with a greater percentage increase of creatinine above baseline (p=0.004, R2= 0.051). There was no significant correlation between incidence (p=0.05) and severity (p=0.47) of aGVHD with lower cyclosporin levels. CMV reactivation was associated with higher cyclosporin levels (p<0.0001). There was no significant difference in cyclosporin levels according to viral copy number (p=0.067). There was no significant difference in cyclosporin levels between disease-relapsed groups and non-relapsed groups (p=0.33). Conclusion Our data suggest that patients who have significant mucositis have lower serum cyclosporin levels with oral cyclosporin dosing, which in turn impact upon post-transplant outcomes, in particular renal impairment and CMV reactivation. References 1. Chaudhry, Hafsa M. et al. "The Incidence And Severity Of Oral Mucositis Among Allogeneic Hematopoietic Stem Cell Transplantation Patients: A Systematic Review." Biology of Blood and Marrow Transplantation 22.4 (2016): 605-616. Web. 2. Blijlevens, N M A, J P Donnelly, and B E de Pauw. "Prospective Evaluation Of Gut Mucosal Barrier Injury Following Various Myeloablative Regimens For Haematopoietic Stem Cell Transplant." Bone Marrow Transplantation 35.7 (2005): 707-711. Disclosures Bajel: AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: travel funding. Ritchie:Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; BMS: Research Funding; Takeda: Research Funding; Beigene: Research Funding; Imago: Research Funding; Novartis: Honoraria; Sanofi: Honoraria.

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A Psychosocial Assessment of Patients before and after Autologous Stem Cell Transplantation.

Blood ◽

10.1182/blood.v104.11.3152.3152 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3152-3152

Author(s):

Brian J. Bolwell ◽

Linda McLellan ◽

Larry Foster ◽

Jane Dabney ◽

Erin Welsh ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Autologous Transplantation ◽

Well Being ◽

Autologous Stem Cell Transplant ◽

Psychosocial Assessment ◽

Cell Transplant ◽

Post Transplant ◽

Allogeneic Bmt ◽

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Abstract There are relatively few reports in the medical literature describing psychosocial assessment of bone marrow transplant patients; what data exists primarily focuses on allogeneic transplant recipients. We have begun to prospectively assess psychosocial parameters of patients undergoing autologous transplantation using the Functional Assessment of Cancer Therapy-BMT (FACT-BMT) tool. The general questions consist of four subscales developed and normed in cancer patients that measure; physical well-being; social/family well-being; emotional well-being; functional well-being; and a specific module to address BMT-specific concerns. Each subscale is positively scored, with higher scores indicating better functioning. A baseline survey is collected by the social worker pre-transplant and a follow-up survey is administered and collected approximately 6 weeks post-transplant by the Transplant Coordinator. 56 consecutive patients undergoing autologous stem cell transplant have FACT-BMT data both pre-transplant and approximately one month post-discharge. Median age was 50. 52% are male; underlying diagnoses include NHL (45%), Hodgkin’s disease (32%), myeloma (16%), AML (5%), testicular cancer (2%). 93% had chemosensitive disease at the time of transplant. All patients received peripheral blood progenitor cells (PBPCs), and all received a chemotherapy-only preparative regimen. All patients were hospitalized for approximately three weeks for the transplant. For most of the variables measured by the FACT-BMT tool, there was no significant difference in pre-transplant and post-transplant scores. The one variable that did change was emotional well-being: patients scored statistically significantly higher post-transplant as compared to the pre-transplant score (p<0.001). We also have collected baseline FACT-BMT data on 42 consecutive allogeneic BMT recipients, as well as 12 recipients of non-myeloablative allogeneic BMT transplants. There is no significant difference in any pre-transplant variables measured by the FACT-BMT score between autologous recipients, ablative allogeneic recipients, and non-myeloablative allogeneic recipients. We conclude that patients undergoing an autologous stem cell transplant have a higher sense of emotional well-being after engraftment and hospital discharge. Presumably this reflects positive feelings about accomplishing this intensive treatment for their underlying malignancy, and suggests that emotional and physical recovery after auto-BMT is reasonably rapid. A larger dataset will hopefully allow a more detailed comparison of allo and auto BMT recipients.

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