scholarly journals Efficacy and Cost Analysis of Eltrombopag in Thrombocytopenia and Poor Graft Function Post Allogeneic Hematopoietic Cell Transplantation in a Canadian Centre - a Prospective Observational Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-18
Author(s):  
RAM V Nampoothiri ◽  
Lina Ho ◽  
Cassandra McEwan ◽  
Ivan Pasic ◽  
Zeyad Al-Shaibani ◽  
...  
Keyword(s):  
Platelet Count ◽  
Cost Analysis ◽  
Supportive Care ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Graft Function ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Poor Graft Function ◽  
The Cost

Background - Thrombocytopenia and poor graft function(PGF) after allogeneic hematopoietic cell transplantation (HCT) may be defined as incomplete count recovery or late cytopenias not due to relapse. There is lack of evidence based treatment for PGF with commonly used modalities being supportive care, second transplants and CD34+ selected stem cell boosts. Eltrombopag, a thrombopoietin receptor agonist, stimulates proliferation and differentiation of hematopoietic stem cells (HSC). It has shown efficacy for PGF in observational studies, but is not approved for this indication. Cost of this drug is a major concern in state sponsored health care systems. Methods - We retrospectively and prospectively collected data about patients who received Eltrombopag for thrombocytopenia and poor graft function after HCT. Post HCT thrombocytopenia was defined as persistent platelet count ≤ 20 x 10^9/l or transfusion dependence. PGF was defined if there was persistence of 2/3 cytopenias: thrombocytopenia, neutropenia (≤ 1.5 x 10^9/l) and/or haemoglobin ≤ 70g/l or transfusion dependence after day 28 of HSCT with complete donor chimerism and no evidence of relapse. Transplant characteristics, post-transplant complications and transfusion history was noted. In treated patients, Eltrombopag was initiated at 50 or 100mg daily and increased every 2 weeks to maximum of 150mg daily based on response. Response criteria: Complete Response (CR) - sustained platelet count ≥ 50 x 10^9/l, haemoglobin≥ 100g/L and ANC ≥ 1.5x10^9/L without transfusions; Partial response (PR) - platelet count 20-50 x 10^9/l or Hb 7-10g/L or ANC 0.5-1.5 x 10^9/l. Cost of transfusions were calculated from estimates of Canadian Blood Services and of hospital admissions were based on local hospital estimates. Cost estimation prior to Eltrombopag was calculated by the cost of supportive care from diagnosis of PGF or thrombocytopenia to initiation of Eltrombopag. Cost estimation post Eltrombopag was done by calculating the cost of drug intake + cost of supportive care (if any) after initiation of Eltrombopag. Primary outcomes were efficacy of drug and transfusion free survival; secondary outcomes were cost comparison between estimated cost prior to Eltrombopag and estimated cost after initiation of Eltrombopag. Results: 15 patients (males 66.67% (n=10); median age - 59 years) received Eltrombopag (Table 1). Indication of Eltrombopag was PGF in 86.7% (n=13) and isolated thrombocytopenia in 13.3% (n=2) patients. Response and cost analysis were limited to the 13 patients with at least 8 weeks follow-up after initiating Eltrombopag. After 8 weeks of Eltrombopag, Overall Response rate(ORR) was 76.9% (n=10; CR = 7; PR = 3). With median follow up of 6.2 months the drug was tapered or discontinued in 60% (n=6) patients showing response. All responders became transfusion independent within 8 weeks of maximum dose of Eltrombopag. The 3-month transfusion free survival after Eltrombopag was 70.7% (Figure 1A). Two out of three patients who did not respond to Eltrombopag died during the study period. The estimated median OS of non-responders vs responders = 12.4 months vs NR; p-0.063; Figure 1B). Eltrombopag was well tolerated with no incidence of serious adverse effects (Liver enzyme elevation, GI toxicity) to report. Rough estimates of cost analysis were done in patients who had response to Eltrombopag. These patients required median (IQR) of 15 (2-25) PRBC transfusions and 46 (32-96) pooled platelet transfusions with median 20 days of hospitalization due to cytopenia complications prior to 4 weeks after starting Eltrombopag. The median (IQR) duration of Eltrombopag exposure was 9.8 (6.3-25.6) weeks. The cost of supportive care before Eltrombopag was marginally higher than calculated total cost of Eltrombopag and subsequent supportive care treatment (Median cost 35311$ vs 33751 $CAD; p=0.9) (Figure 1C). The crude cost estimate of supportive care did not include cost estimates of human resources (including nursing), hospital visit time, time off work, and quality of life. Conclusion - Eltrombopag is a safe and efficacious therapy for thrombocytopenia and poor graft function after allogeneic HCT with response in 77% of patients. Preliminary cost analysis shows that Eltrombopag is cost neutral by reducing supportive care and hospitalization costs and may be especially relevant in countries where supply of safe and adequate blood products is a challenge. Figure Disclosures Lipton: Ariad: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Mattsson:ITB: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Mallinkrodt: Honoraria; Jazz Pharmaceuticals: Honoraria; Gilead: Honoraria. OffLabel Disclosure: Eltrombopag is approved for ITP and Aplastic Anemia. It is currently not approved for thrombocyotpenia and poor graft function after Allogeneic Hematopoietic Cell Transplantation in Canada.

scholarly journals Poor Outcomes of HLA-Mismatched Allogeneic Hematopoietic Cell Transplantation and High Ferritin Levels after a Reduced-Intensity Conditioning Regimen in Patients with Advanced Myelofibrosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5742-5742
Author(s):  
Han Bi Lee ◽  
Jae-Ho Yoon ◽  
Gi June Min ◽  
Sung-Soo Park ◽  
Silvia Park ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Advisory Committees ◽  
Reduced Intensity

Allogeneic hematopoietic cell transplantation (allo-HCT) preconditioning intensity, donor choice, and graft-versus-host disease (GVHD) prophylaxis for advanced myelofibrosis (MF) have not been fully elucidated. Thirty-five patients with advanced MF were treated with reduced-intensity conditioning (RIC) allo-HCT. We searched for matched sibling (n=16) followed by matched (n=10) or mismatched (n=5) unrelated and familial mismatched donors (n=4). Preconditioning regimen consisted of fludarabine (total 150 mg/m2) and busulfan (total 6.4 mg/kg) with total body irradiation≤ 400cGy. All showed engraftments, but four (11.4%) showed either leukemic relapse (n=3) or delayed graft failure (n=1). Two-year overall survival (OS) and non-relapse mortality (NRM) was 60.0% and 29.9%, respectively. Acute GVHD was observed in 19 patients, and grade III-IV acute GVHD was higher with HLA-mismatch (70% vs. 20%, p=0.008). Significant hepatic GVHD was observed in nine patients (5 acute, 4 chronic), and six of them died. Multivariate analysis revealed inferior OS with HLA-mismatch (HR=6.40, 95%CI 1.6-25.7, p=0.009) and in patients with high ferritin level at post-HCT D+21 (HR=7.22, 95%CI 1.9-27.5, p=0.004), which were related to hepatic GVHD and high NRM. RIC allo-HCT can be a valid choice for advanced MF. However, HLA-mismatch and high post-HCT ferritin levels related to significant hepatic GVHD should be regarded as poor-risk parameters. Disclosures Kim: Handok: Honoraria; Amgen: Honoraria; Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hanmi: Consultancy, Honoraria; AGP: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; SL VaxiGen: Consultancy, Honoraria; Novartis: Consultancy; Janssen: Honoraria; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Honoraria; BL & H: Research Funding; Chugai: Honoraria; Yuhan: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lee:Alexion: Consultancy, Honoraria, Research Funding; Achillion: Research Funding.

Brentuximab Vedotin (SGN-35) Enables Successful Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Relapsed/Refractory Hodgkin Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 664-664 ◽  
Author(s):  
Robert W. Chen ◽  
Stephen J. Forman ◽  
Joycelynne Palmer ◽  
Ni-Chun Tsai ◽  
Leslie Popplewell ◽  
...  
Keyword(s):  
Disease Control ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Infectious Complications ◽  
Brentuximab Vedotin ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Antibody Drug Conjugate

Abstract Abstract 664 Background: The prognosis of patients with Hodgkin lymphoma (HL) who relapse following autologous hematopoietic cell transplantation is poor. Although reduced intensity allogeneic hematopoietic cell transplantation (RIC allo-HCT) can induce durable remissions in some patients with relapsed/refractory HL, its use is limited by a lack of disease control prior to transplantation. Brentuximab vedotin (b-vedotin, SGN-35), a novel antibody-drug conjugate, has a 75% objective response rate in patients with relapsed/refractory HL (Chen 2011). To examine the impact of b-vedotin on RIC allo-HCT, we performed a retrospective analysis of relapsed/refractory HL patients who received b-vedotin at City of Hope National Medical Center (COH) and Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA) and then went on to receive RIC allo-HCT. Methods: Between October 2008 and July 2011, 46 patients with relapsed/refractory HL received b-vedotin at COH and SCCA through Seattle Genetics trials (SGN-35-03, 06, 07, and 08). 16/46 (34.8%) patients subsequently underwent RIC allo-HCT, including 12 at COH (2/12 were transplanted at University of Utah and Wellington Hospital) and 4 at the SCCA. The baseline characteristics are listed in Table 1. All 12 COH patients received fludarabine/melphalan as the conditioning regimen, 5/12 used matched related donors and 7/12 used matched unrelated donors. 10/12 received tacrolimus/sirolimus as graft-versus-host disease (GVHD) prophylaxis and 2 patients received mycophenolate mofetil (MMF) and cyclosporine (CSP). In contrast, 3/4 patients transplanted at the SCCA received haploidentical donors transplantation using fludarabine/cytoxan/2Gy TBI conditioning and cytoxan/tacrolimus/MMF as GVHD prophylaxis while 1/4 underwent conditioning using 2Gy TBI followed by CSP/MMF prophylaxis. Patients were monitored for engraftment, aGVHD, cGVHD, chimerism, and infectious complications per institutional standards. Each institutional review board approved the retrospective analysis of individual center data and we plan to present combined analysis of COH/SCCA data at ASH. Results: At COH, the 1 year PFS was 90% (95% CI: 54.0, 98.2) and the 1 year OS was 100% with a median follow-up of 13.2 months (range: 2, 20), In addition, the 1 year relapse rate was 10% (95% CI: 1.7, 46) and the non-relapse mortality at 1 year was 0%. Likewise, all 4 of the SCCA patients are alive and progression-free with a median follow up of 7.2 months (range: 2.9, 19). For the entire cohort the rates of aGVHD and cGVHD were 25% and 63%, respectively. There was no grade III-IV aGVHD and only 1/16 (6.3%) with extensive cGVHD. There was no delay of engraftment or increased incidence of CMV/EBV infections (Table 1). The only patient who relapsed after RIC allo-HCT had progressive disease at the time of transplantation, and 276 days had elapsed between the last dose of b-vedotin to RIC allo-HCT. Conclusion: These data suggest that b-vedotin prior to RIC allo-HCT in HL can yield prolonged disease control without a delay in engraftment, increase in non-relapse mortality, aGVHD, cGVHD, and post transplant infectious complications. Such a strategy may allow more patients with relapsed or refractory HL to gain sufficient pre-transplant disease control to undergo this potentially curative procedure. Disclosures: Chen: Seattle Genetics: Consultancy, Research Funding. Off Label Use: SGN-35, a novel antibody drug conjugate, is used as salvage therapy for relapsed hodgkin lymphoma prior to allogeneic hematopoietic cell transplantation. Grove:seattle genetics: Employment. Gopal:Bio Marin: Research Funding; SBio: Research Funding; Pfizer: Research Funding; Abbott: Research Funding; Millenium: Honoraria, Speakers Bureau; Cephalon: Research Funding; Piramal: Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Spectrum: Research Funding; GSK: Research Funding; Biogen-Idec: Research Funding.

Impact of New Anti-Leukemia Agents on Transplant Outcomes in Adults with Acute Lymphoblastic Leukemia (ALL) Undergoing Allogeneic Hematopoietic Cell Transplantation (HCT) in Second Complete Remission

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4676-4676 ◽  
Author(s):  
Sara Lozano Cerrada ◽  
David Marin ◽  
Gabriela Rondon ◽  
Celina Ledesma ◽  
Uday R. Popat ◽  
...  
Keyword(s):  
T Cell ◽  
Complete Remission ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Transplant Outcomes ◽  
Equity Ownership

Abstract Introduction: The number of available salvage agents for patients with relapsed ALL has significantly increased in the last 5 years. Furthermore, these recent therapies, such as antibody and T-cell therapy, have a distinct mechanism of action and toxicity profile compared to conventional multi-drug chemotherapy combinations which have been the mainstay of ALL treatment. We sought to investigate the potential efficacy and toxicity of these agents when used prior to allogeneic hematopoietic cell transplantation (HCT), and to compare overall transplant outcomes with these different types of therapies. Methods: 126 consecutive patients with ALL in second complete remission (CR2) underwent HCT at MD Anderson Cancer Center between January 2004 and December 2015. The patient and transplant characteristics are described in Table 1. The probabilities of outcomes were calculated with the Kaplan-Meyer method. Variables found to be significant at the p<0.1 level were included in a Cox regression multivariate model. All p values are two sided. Results: With a median follow-up of 38.4 months (range 6-125), the 3-year overall survival(OS), progression-free survival (PFS) and transplant-related mortality (TRM) rates were 34.6%, 29.5% and 33.2%, respectively, for the entire group. Patients receiving well-matched transplant donors fared better than those receiving mismatched donors (Figure 1). Second CR was attained in 104 patients with the first line of salvage therapy. Salvage therapy consisted of HyperCVAD-based chemotherapy alone in 57 patients, chemotherapy plus tyrosine kinase inhibitors (TKI) in 18, chemotherapy plus rituximab in 11, chemotherapy plus inotuzumab in 5, inotuzumab monotherapy in 12, and blinatumomab monotherapy in one patient. We found no statistical difference in OS, PFS or TRM following transplant based on these prior therapies. Furthermore, we found no difference in the expected probabilities of acute or chronic GVHD. In the 8 patients treated with blinatumomab monotherapy for first or subsequent salvage, all 8 progressed following transplant at a median of 4.5 months. Eight out of 126 (6.3%) patients developed VOD; 3 out of 26 (11.5%) patients treated with inotuzumab developed VOD, but this did not impact TRM post HCT compared with other treatment groups. Conclusions: Transplant outcomes were not different following antibody or T-cell salvage therapy as compared to conventional chemotherapy in this single center, retrospective study. Larger numbers of patients will need to be studied as we continue to incorporate these newer therapies into our treatment regimens. Disclosures Ciurea: Cyto-Sen Therapeutics: Equity Ownership; Spectrum Pharmaceuticals: Other: Advisory Board. Jabbour:BMS: Consultancy; ARIAD: Consultancy; Pfizer: Research Funding; Pfizer: Consultancy; Novartis: Research Funding; ARIAD: Research Funding. Kantarjian:ARIAD: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Research Funding; Pfizer Inc: Research Funding; Delta-Fly Pharma: Research Funding; Novartis: Research Funding. Champlin:Ziopharm Oncology: Equity Ownership, Patents & Royalties; Intrexon: Equity Ownership, Patents & Royalties.

scholarly journals Higher Efficacy of TBI + Cyclophosphamide Than TBI + Fludarabine As Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia: An Analysis By the Acute Leukemia Working Party of the EBMT

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2876-2876
Author(s):  
Sebastian Giebel ◽  
Myriam Labopin ◽  
Gerard Socie ◽  
Mahmoud Aljurf ◽  
Urpu Salmenniemi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Lymphoblastic Leukemia ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Karnofsky Performance Score ◽  
Increased Risk

Abstract BACKGROUND: Allogeneic hematopoietic cell transplantation (allo-HCT) is a standard of care for adults with high-risk acute lymphoblastic leukemia (ALL) in first or subsequent complete remission (CR). Myeloablative total body irradiation (TBI) combined with cyclophosphamide (Cy) is the most frequently used conditioning regimen. In order to reduce toxicity Cy may be replaced by fludarabine (Flu). The goal of this registry-based, retrospective study was to compare outcomes of allo-HCT following TBI/Cy vs. TBI/Flu conditioning. PATIENTS AND METHODS: Included in the analysis were 2255 patients aged 18-65 years, treated with allo-HCT from either a matched sibling (43%) or unrelated (57%) donor in CR1 (83%) or CR2 (17%), between the years 2010-2020. Patients with Ph(-) B-ALL, Ph(+) B-ALL, and T-ALL were represented in equal proportions. TBI 12Gy + Cy was used in 2105 cases while TBI 12Gy + Flu was administered to 150 patients. Patients treated with TBI/Flu were significantly older (median 35 years vs. 33 years, p=0.006), with poorer Karnofsky performance score (&lt;90, 27% vs. 20%, p=0.03), more frequently transplanted from unrelated donors (71% vs. 57%, p=0.0007) with less frequently use of bone marrow as a source of stem cells (5% vs. 21%, p&lt;0.0001), and in more recent year (median 2018 vs. 2015, p&lt;0.0001). RESULTS: Engraftment rate was 99% for both TBI/Cy and TBI/Flu patients. In a univariate analysis the use of TBI/Cy as compared to TBI/Flu was associated with a tendency to reduced incidence of relapse (24% vs. 29% at 2 years, p=0.1), increased incidence of grade 2-4 acute graft versus host disease (GVHD, 35.5% vs. 28%, p=0.08) and improved leukemia-free survival (LFS, 62% vs. 57%, p=0.18). The rates and causes of non-relapse mortality (NRM) did not differ significantly between the two conditioning groups. In a multivariate model adjusted for other prognostic factors, TBI/Cy conditioning was associated with reduced risk of relapse (HR=0.69, p=0.049) and increased risk of grade 2-4 acute GVHD (HR=1.57, p=0.03) without significant effect on other transplantation outcomes. An additional analysis was performed with TBI/Cy treated patients (n=132) matched strictly to those treated with TBI/Flu (n=132) in terms of disease subtype, disease status and donor type with the nearest neighbor for patient age, patient and donor sex, in vivo T-cell depletion, Karnofsky score and source of stem cells; the use of TBI/Cy as compared to TBI/Flu was associated with significantly reduced rate of relapse (18% vs. 30% at 2 years, p=0.015) and a tendency to an improved LFS (65% vs. 59%, p=0.07) and overall survival (OS, 73% vs. 68%, p=0.16) without effect on NRM and GVHD. CONCLUSIONS: The use of myeloablative TBI/CY as conditioning prior to allo-HCT for adult patients with ALL in CR1 or CR2 is associated with stronger anti-leukemic effect leading to significantly lower relapse rate compared to TBI/Flu and therefore should be likely considered a preferable regimen. Disclosures Giebel: Janssen: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Labopin: Jazz Pharmaceuticals: Honoraria. Socie: Alexion: Research Funding. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Kröger: Novartis: Research Funding; Riemser: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Gilead/Kite: Honoraria; Celgene: Honoraria, Research Funding; AOP Pharma: Honoraria. Forcade: Novartis: Consultancy, Other: Travel Support, Speakers Bureau; Gilead: Other: Travel Support, Speakers Bureau; Jazz: Other: Travel Support, Speakers Bureau; MSD: Other: Travel Support. Huynh: Jazz Pharmaceuticals: Honoraria. Spyridonidis: Menarini: Current Employment. Perić: therakos: Honoraria; servier: Honoraria; MSD: Honoraria; Astellas: Honoraria; NOVARTIS: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria. Mohty: Pfizer: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Astellas: Honoraria; Gilead: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria; Bristol Myers Squibb: Honoraria; Takeda: Honoraria; Sanofi: Honoraria, Research Funding; Adaptive Biotechnologies: Honoraria.

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.

Supportive Care Only Versus Allogeneic Hematopoietic Cell Transplantation in Patients ≥ 60 Years with De Novo High-Risk MDS.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 596-596
Author(s):  
Uwe Platzbecker ◽  
Jürgen Finke ◽  
Rudolf Trenschel ◽  
Schaefer-Eckart Kerstin ◽  
Martin Bornhauser ◽  
...  
Keyword(s):  
High Risk ◽  
Supportive Care ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
De Novo ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Matched Pair ◽  
Allogeneic Hct ◽  
Blast Count

Abstract Abstract 596 Myelodysplastic syndromes (MDS) occur primarily in older patients, and allogeneic hematopoietic cell transplantation (HCT) only infrequently is considered a therapeutic option. Until recently best supportive care (BSC), only including transfusion support, has been the standard of care for the majority of these patients (pts). Novel treatment modalities and innovations in transplant protocols have changed that approach and have led to increased frequency of allogeneic HCT in pts more than 60 or 65 years of age. However, no randomized trial comparing outcomes with BSC and allogeneic HCT has been conducted. Therefore, we performed a matched pair analysis including 126 patients 60-77 (median 65) years old with de novo high-risk MDS by FAB classification (RAEB n=88, RAEB-t n=20, CMML n=18) who underwent allogeneic HCT at a median of 8.6 months from initial MDS diagnosis. Cytogenetics were availabel in 108 pts (good: n=63, intermediate: n=18, poor: n=27), allowing for IPSS scoring in 107 pts: 28 were INT-1, 45 INT-2, and 34 HIGH risk. Before HCT most pts had progressed to more advanced disease (RAEB n=45, RAEB-t n=10, CMML n=10, AML n=61). At the time of HCT the median blast count in the marrow was 12%. While 51 pts had received supportive care only prior to HCT the remaining had undergone chemotherapy of various intensities including methyltransferase-inhibitors (n=10). Patients were prepared for HCT with one of several reduced intensity (RIC, n=79) or more conventional intensity (CI, n=47) conditioning regimens and transplanted from related (n=50) or unrelated (n=76) donors. The outcome after HCT was compared to outcome with BSC only in a matched pair group from the Düsseldorf registry. Matching criteria were age, gender, marrow blast count, FAB and IPSS category. One prerequisite was that controls were still under supportive care at the time of HCT of the corresponding matched patient. With a median follow-up of 60 months from MDS diagnosis the 5-year overall survival (OS) rate was 45% for the HCT and 25% for the BSC cohort (p=0.008). These retrospective data suggest, therefore, that allogeneic HCT from related or unrelated donors, using various conditioning approaches, compared to BSC only, offers a meaningful survival advantage and the potential of cure for 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 allogeneic HCT within the growing therapeutic opportunities for pts with MDS. Disclosures: No relevant conflicts of interest to declare.

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