scholarly journals Measles Reactivity in Windsor Patients Post Autologous Versus Allogeneic Hematopoietic Cell Transplantation: A Retrospective Review

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 30-30
Author(s):  
Kayla Negus ◽  
Mohammad Jarrar ◽  
Indryas L. Woldie ◽  
Sindu M. Kanjeekal ◽  
Kit McCann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Hematopoietic Cell Transplantation ◽  
Cellular Therapy ◽  
Immune Status ◽  
The United States ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Post Transplant ◽  
Allogeneic Hct ◽  
Autologous Hct

Background As the antivaccine movement has increased, vaccine preventable illnesses have also increased. The resurgence of measles globally has been noted, specifically the United States received 1200 new cases of measles in 2019, which is the highest number of cases since 1994. Measles is a highly contagious pathogen; the virus has an attack rate of up to 90% in susceptible individuals. Standard of care for patients post hematopoietic cell transplant (HCT) includes repeating all childhood vaccinations. However, compliance with recommendations is unknown. No previous reports have been created measuring the difference in measles, mumps, and rubella (MMR) reactivity between autologous and allogeneic HCT patients post treatment. Methods A retrospective chart review investigated HCT patients between 2000-2019 from the Windsor Regional Hospital (WRH) cancer centre. Patients were excluded from data collection if they were deceased before an MMR reactivity test could be done or if they were lost to follow up. A total of 83% of autologous HCT (N=57) and 66% of allogeneic HCT (N=47) patients had serology tested to measure MMR reactivity post-transplant prior to live vaccinations. MMR titres were drawn from autologous patients a median of 395 days after HCT and a median of 907 days after HCT for allogeneic patients. Results Overall, allogeneic HCT patients had more reactivity than autologous HCT patients as seen in Table 1. Conclusion All patients not reactive to measles need to be re-vaccinated 24 months after treatment according to 2019 American Society for Transplantation and Cellular Therapy guidelines. Our patients are treated in a variety of transplant centers in Ontario, Canada as well as Detroit, Michigan; which is of concern because measles cases have been reported in Detroit. The majority (66%) of allogeneic HCT patients had a myeloid malignancy, while 70% of autologous patients has a diagnosis of multiple myeloma. As evidenced by the poor MMR response, less robust immune systems may be accounted for by multiple myeloma patients. This does emphasize the need for MMR vaccinations post HCT for multiple myeloma patients and raises the question regarding immunization for at risk non-transplant eligible patients. We suggest that it may be reasonable to assess MMR immune status in all myeloma patients to determine if this is a transplant effect or an effect of the underlying immune status of the myeloma patient. This study does emphasize the need to assess MMR status post transplant in all myeloma patients, as the vast majority in our study did not demonstrate immunity post stem cell transplant. Figure Disclosures Hamm: Amgen: Consultancy.

Allogeneic hematopoietic cell transplant for multiple myeloma: Comparative results of planned therapy versus salvage therapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7035-7035
Author(s):  
L. Shune ◽  
D. J. Weisdorf ◽  
B. McClune ◽  
L. Ma ◽  
L. J. Burns ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Salvage Therapy ◽  
Therapy Group ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hct ◽  
Autologous Hct ◽  
Related Mortality

7035 Background: Despite advances in therapy for multiple myeloma, the disease remains incurable using chemotherapy or immune-modulating agents alone. Several newer hematopoietic cell transplant (HCT) strategies including tandem HCT, and non- myeloablative (NMA) regimens have reported encouraging results. However, the appropriate timing for utilizing these strategies is not clear. Methods: We report outcomes in 51 patients with multiple myeloma who received an allogeneic HCT; either as salvage therapy (after failing a prior autologous HCT), n= 15 or as planned therapy, n= 36, between the years 1996 and 2008 at University of Minnesota. Results: Patients in salvage therapy group were significantly older than in planned therapy group (median age 58 versus 49 years) and had a longer interval from diagnosis to transplant (median 47 versus 10 months). Forty four patients received a HCT from a HLA-identical sibling. Five received umbilical cord blood (four in salvage therapy, one in planned therapy group) and two received unrelated donor HCT (one in each group). Thirteen patients in planned therapy group underwent a tandem transplant (planned autologous followed by NMA sibling HCT). All patients in salvage therapy group, and 50% in planned therapy group received NMA HCT. Patients in salvage therapy group were more heavily pre-treated, all having failed a prior autologous HCT. Complete response was seen in 34% versus 47% of recipients in the two groups, respectively. After a median follow-up of 24 and 41 months, similar relapse was seen, but transplant related mortality (TRM) was significantly higher in salvage therapy group, leading to significantly lower two year survival and disease free survival (DFS) in salvage group. Conclusions: Good overall survival and low transplant related mortality was seen in patients undergoing a planned allogeneic transplant. In heavily pre-treated patients, receiving allogeneic HCT as salvage therapy, despite lower relapse, the high TRM led to lower survival. [Table: see text] No significant financial relationships to disclose.

scholarly journals Management of Herpesvirus Infections in Hematopoietic Cell Transplant Recipients

2021 ◽  
Vol 2 (1) ◽  
pp. 8-21
Author(s):  
Jan Styczynski
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Cellular Therapy ◽  
Hematopoietic Cell ◽  
Host Cells ◽  
Preventive Strategy ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Screening Assay ◽  
Specific Level

Following primary infection, herpesviruses establish latency in infected individuals in the host cells and may reactivate upon external stimuli and during periods of immunosuppression. The objective of this paper was to the present current strategies on preventive and therapeutic management of infections with herpesviruses in recipients of hematopoietic cell transplantation. Strategies of antiviral management include prophylaxis, pre-emptive treatment and targeted treatment. Empirical therapy is not used in antiviral strategies. Prophylaxis can be done at universal (preventive strategy) and specific level. Universal prophylaxis includes non-pharmacologic methods of prevention of infection or reactivation. Risk-adapted specific prophylaxis includes use of specific antivirals or cellular therapy or other specific methods in order to prevent specific infection, in high-risk groups. Pre-emptive therapy means use of therapeutic approaches in asymptomatic infection, detected by a screening assay. Targeted therapy is used in established specific viral end-organ infections. The following sections of the paper refer to prophylaxis and treatment strategies, respectively, against CMV, EBV, HSV, VZV, HHV-6, HHV-7, and HHV-8 after allogeneic hematopoietic cell transplantation.

Hematopoietic Cell Transplantation for Benign Hematological Disorders and Solid Tumors

Hematology ◽  
2003 ◽  
Vol 2003 (1) ◽  
pp. 372-397 ◽  
Author(s):  
Rainer F. Storb ◽  
Guido Lucarelli ◽  
Peter A. McSweeney ◽  
Richard W. Childs
Keyword(s):  
Autoimmune Diseases ◽  
Aplastic Anemia ◽  
Solid Tumors ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Family Members ◽  
Hematopoietic Cell ◽  
Allogeneic Hct ◽  
The Status ◽  
Autologous Hct

Abstract Allogeneic hematopoietic cell transplantation (HCT) has been successfully used as replacement therapy for patients with aplastic anemia and hemoglobinopathies. Both autologous and allogeneic HCT following high-dose chemotherapy can correct manifestations of autoimmune diseases. The impressive allogeneic graft-versus-tumor effects seen in patients given HCT for hematological malignancies have stimulated trials of allogeneic immunotherapy in patients with otherwise refractory metastatic solid tumors. This session will update the status of HCT in the treatment of benign hematological diseases and solid tumors. In Section I, Dr. Rainer Storb reviews the development of nonmyeloablative conditioning for patients with severe aplastic anemia who have HLA-matched family members. He also describes the results in patients with aplastic anemia given HCT from unrelated donors after failure of responding to immunosuppressive therapy. The importance of leuko-poor and in vitro irradiated blood product transfusions for avoiding graft rejection will be discussed. In Section II, Dr. Guido Lucarelli reviews the status of marrow transplantation for thalassemia major and updates results obtained in children with class I and class II severity of thalassemia. He also describes results of new protocols for class III patients and efforts to extend HCT to thalassemic patients without HLA-matched family members. In Section III, Dr. Peter McSweeney reviews the current status of HCT for severe autoimmune diseases. He summarizes the results of autologous HCT for systemic sclerosis, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus, and reviews the status of planned Phase III studies for autologous HCT for these diseases in North America and Europe. He also discusses a possible role of allogeneic HCT in the treatment of these diseases. In Section IV, Dr. Richard Childs discusses the development and application of nonmyeloablative HCT as allogeneic immunotherapy for treatment-refractory solid tumors. He reviews the results of pilot clinical trials demonstrating graft-versus-solid tumor effects in a variety of metastatic cancers and describes efforts to characterize the immune cell populations mediating these effects, as well as newer methods to target the donor immune system to the tumor.

scholarly journals Comparison of the Impact of Pre-Transplant Co-Morbidity Scores on Allogeneic Hematopoietic Stem Cell Transplant Outcomes

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4670-4670
Author(s):  
Mohammed A. Marei ◽  
Eshetu G Atenafu ◽  
Arjun Law ◽  
Wilson Lam ◽  
Rajat Kumar ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Post Transplant ◽  
Transplant Outcomes ◽  
C Statistic ◽  
Co Morbidity ◽  
The Impact

Abstract Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for the treatment of various hematological diseases, in part due to the effect of conditioning chemotherapy, and in part due to graft-versus-malignancy effect. However, alloHCT is associated with significant morbidity and mortality. Multiple co-morbidity indices have been published in the literature for the purpose of pre-transplant risk assessment. The purpose of the presented study is to assess a number of these pre-transplant scores on a single-center transplant population and to determine the score with improved risk stratification ability using concordance statistics. Methods: We investigated the impact of the prospectively collected Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) on post-transplant outcomes for 243 recipients of allo-HCT performed between August 2014 and October 2016 at the Princess Margaret Cancer Center (Toronto, Canada), and compared this score to other pre-transplant scores including the age-adjusted HCT-CI, PAM score (Pre-transplant Assessment of Mortality Score) and the Disease Risk Index (DRI). Partitioning of the HCT-CI, HCT-CI/age and PAM scores into three groups was performed based on maximum significant differences on univariate analysis for overall survival (OS). Concordance statistics were used to compare the stratification power of the scores. Statistical analyses were performed using SAS version 9.4 (SAS Institute, Inc, Cary, NC). Results: The median age at transplant is 56 years, patients were transplanted for AML (53%), ALL (7.5%), MDS (13.5%), MPN (14%), NHL/CLL (8.5%) and (3.5%) AA. Donors were matched related in 37%, unrelated in 59% and haploidentical in 3% of the patients. Reduced intensity conditioning chemotherapy was used in 132 patients (54%), 153 patients (63%) received in-vivo T-cell depletion by using Campath or ATG, both donor and recipient were CMV negative in 48 (20%) of the patients. DRI was high in 67 (29%), intermediate in 145 (62%) and low in 22 (9%) of patients. HCT-CI was 0 in 90 (37%), 1 in 49(21%) and ≥2 in 103 (43%) of patients. HCT-CI/age was 0 in 22 (10%), 1 in 72 (30%) and ≥2 in 148 (62%). PAM score was 1-17 in 157(68%), 18-24 in 70 (30%) and 25-27 in 7 (3%) of patients. Median follow up of survivors was 28 months (range 17-44 months). OS of the entire cohort was 51% and 43% at 2 and 5 years post-transplant respectively. Cumulative incidence of relapse (CIR) was 19% at 2 years. For OS, as grouped above, the DRI did not demonstrate a significant difference between groups (p=0.77). For HCT-CI, p=0.034 (Figure 1), for HCT-CI/age p=0.02 and for the PAM score p=0.38. For OS, for the DRI, the C-statistic was 0.51 (se=0.03, 95%CI 0.45-0.57). For the PAM score, C-statistic was 0.51 (se=0.02,95%CI 0.45-0.56). For the HCT-CI age, C-statistic was 0.56 (se=0.024, 95%CI 0.51-0.61). For the HCT-CI, C-statistic was 0.56 (se 0.02, 95% CI 0.50-0.61). For CIR, the PAM score demonstrated a superior C-statistic of 0.56 (se=0.06, 95%CI 0.44-0.67) compared to the other scores. For NRM, the HCT-CI score (Figure 2, p=0.039) is superior with C-statistic 0.56 (se=0.04, 95%CI=0.49-0.63). Conclusion: Based on the above described analysis, the original HCT-CI score as described by Sorror et aldemonstrates superior prognostic stratification ability for OS and NRM in our patient cohort compared to other scores. Further investigation for the development of an optimal risk scoring system for allogeneic HCT is required. Figure 1. Figure 1. Disclosures Kim: Paladin: Consultancy; Pfizer: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding. Lipton:Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding.

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.

scholarly journals A Portrait of SARS-CoV-2 Infection in Patients Undergoing Hematopoietic Cell Transplantation: A Systematic Review of the Literature

2022 ◽  
Vol 29 (1) ◽  
pp. 337-349
Author(s):  
Adrian J. M. Bailey ◽  
Aidan M. Kirkham ◽  
Madeline Monaghan ◽  
Risa Shorr ◽  
C. Arianne Buchan ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Performance Status ◽  
Treatment Options ◽  
Signs And Symptoms ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Newcastle Ottawa Scale ◽  
Special Challenge ◽  
Autologous Hct

The management of COVID-19 in hematopoietic cell transplant (HCT) recipients represents a special challenge given the variable states of immune dysregulation and altered vaccine efficacy in this population. A systematic search (Ovid Medline and Embase on 1 June 2021) was needed to better understand the presenting features, prognostic factors, and treatment options. Of 897 records, 29 studies were identified in our search. Most studies reporting on adults and pediatric recipients described signs and symptoms that were typical of COVID-19. Overall, the mortality rates were high, with 21% of adults and 6% of pediatric HCT recipients succumbing to COVID-19. The factors reported to be associated with increased mortality included age (HR = 1.21, 95% CI 1.03–1.43, p = 0.02), ICU admission (HR = 4.42, 95% CI 2.25–8.65, p < 0.001 and HR = 2.26, 95% CI 1.22–4.20, p = 0.01 for allogeneic and autologous HCT recipients), and low platelet count (OR = 21.37, 95% CI 1.71–267.11, p = 0.01). Performance status was associated with decreased mortality (HR = 0.83, 95% CI 0.74–0.93, p = 0.001). A broad range of treatments was described, although no controlled studies were identified. The risk of bias, using the Newcastle–Ottawa scale, was low. Patients undergoing HCT are at a high risk of severe morbidity and mortality associated with COVID-19. Controlled studies investigating potential treatments are required to determine the efficacy and safety in this population.

scholarly journals Health Care Reimbursement and Service Utilization Among Medicare Beneficiaries with Multiple Myeloma Receiving Autologous Hematopoietic Cell Transplantation in Inpatient and Outpatient Settings

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 832-832 ◽  
Author(s):  
Neil Dunavin ◽  
Lih-Wen Mau ◽  
Christa Lea Meyer ◽  
Clint Divine ◽  
Al-Ola Abdallah ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Transplantation ◽  
Service Utilization ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Lower Percentage ◽  
Medicare Beneficiaries ◽  
Factors Associated ◽  
Autologous Hct ◽  
Autologous Hematopoietic Cell Transplantation

Abstract Introduction: Inpatient services are the leading drivers of cost for autologous hematopoietic cell transplantation (HCT), and the number of Medicare beneficiaries who receive autologous HCT is increasing. Using a merged dataset of Center for International Blood and Marrow Transplant Research (CIBMTR) transplant and outcomes data and Centers for Medicare and Medicaid Services (CMS) Medicare administrative claims data, we examined reimbursement and service utilization among Medicare beneficiaries with multiple myeloma (MM) who received IP and OP autologous HCT. Methods: This was a multicenter retrospective cohort study. A total of 11,358 HCT recipients from 2010-2012 were identified in the CMS Medicare database; 9,055 (80%) were linked with CIBMTR data. Selection criteria included first HCT for MM, diagnosis-to-HCT time between 0 and 18 months, and continuous enrollment for 30 days prior to index and 100 days post-HCT or until death. For IP-HCT, the index period for reimbursement and service utilization was day of admission for HCT through discharge date. For OP-HCT, the index period was day -2 through HCT date to capture the conditioning regimen. Total IP and OP service days from 30 days prior to index and 100 days post-HCT, and subsequent admissions post the HCT index period were calculated. Total reimbursement consisted of all payments made to providers (Medicare payments for Part A & B services, secondary payer, and patient responsibility of deductibles, coinsurance, and copayments), which was adjusted by a weighted generalized linear model (GLM). Patient responsibility was assessed separately and adjusted by the same GLM. Kaplan-Meier method was used for overall survival (OS) analysis; potential factors associated with OS were adjusted by Cox regression modeling. Results: The final cohort comprised 1,640 patients; 1,445 (88%) received IP-HCT (126 centers) and 195 (12%) OP-HCT (24 centers). Patient characteristics, functional status, disease status, and HCT year were similar between groups except a higher percentage of IP-HCT recipients were 70 years and older (IP-HCT: 31%, OP-HCT: 19%; P=0.0003), and a lower percentage of IP-HCT recipients received full dose melphalan 200 mg/m2 (IP-HCT: 68%, OP-HCT: 90%; P=0.0036). There was a significant difference between the cohorts in the utilization of IP services (IP-HCT group: median 19 days, OP-HCT group: 4 days; P < 0.0001) and OP services (IP-HCT group: median 16 days, OP-HCT group: 33 days; P < 0.0001) at day 100. Adjusted total mean reimbursement for the IP-HCT group ($83,380 [95% CI: $78,958-$88,051]) was higher than the OP-HCT group ($55,721 [95% CI: $38,595-$80,446]) (P= 0.0301) (Figure). Factors associated with total reimbursement in the GLM were transplant setting, age, sex, comorbidity index, diagnosis-to-HCT time, and melphalan dose. Adjusted total patient responsibility for the IP-HCT group was $4,567 (95% CI: $4,210- $4,955) and $7,372 ($4,218- $12,884) (P=0.0902) for the OP-HCT group. Within 100 days post-HCT, 107/195 (55%) OP-HCT recipients had at least one subsequent admission, compared to 348/1,445 (24%) IP-HCT recipients (P < 0.0001). OS at 100 days was high for both HCT settings and adjusted OS was not significantly different by transplant setting (IP-HCT 98% [95% CI: 97%-99%]; OP-HCT 99% [95% CI: 98%-100%; P=0.1903) Conclusions: Reimbursement and service utilization varied by HCT setting for Medicare beneficiaries with MM. Total reimbursement for 100 days post-HCT was $27,659 higher for IP-HCT than OP-HCT, after adjusting for patient and HCT-related characteristics. After the HCT index period, approximately 1 in 4 IP-HCT recipients required re-hospitalization within 100 days, whereas 1 in 2 OP-HCT recipients required subsequent hospitalization. Many factors influence the decision between IP or OP autologous HCT, including: center experience, severity of disease, patient co-morbidities, access to caregivers, proximity of lodging, cost to the patient, and reimbursement for services to the hospital system. The CIBMTR-CMS merged database is a new resource to support ongoing efforts to inform transplant centers and healthcare systems about provision of care options in the Medicare population. Figure. Figure. Disclosures Ganguly: Janssen: Consultancy; Amgen: Consultancy; Seattle Genetics: Speakers Bureau; Daiichi Sankyo: Research Funding.

scholarly journals Panobinostat As a Maintenance Therapy after Autologous Hematopoietic Cell Transplantation for Patients with Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3189-3189
Author(s):  
Taiga Nishihori ◽  
Rachid Baz ◽  
Leonel Ochoa ◽  
Omar Alexis Castaneda Puglianini ◽  
Kenneth H. Shain ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Advisory Committees ◽  
Autologous Hct ◽  
Autologous Hematopoietic Cell Transplantation

Background: Autologous hematopoietic cell transplantation (HCT) followed by maintenance therapy with an immunomodulatory agent or a proteasome inhibitor remains an important strategy for upfront treatment in multiple myeloma (MM) with progression-free survival (PFS) and overall survival (OS) advantage. We designed a two-arm, open-label prospective study to examine the safety and tolerability of two different dosing schedules of an oral pan-histone deacetylase inhibitor, panobinostat (pano) as an alternative maintenance therapy option in patients with MM (NCT02722941). Methods: A total of 30 MM patients who underwent autologous HCT within the preceding 90 to 180 days were enrolled at Moffitt Cancer Center using a sequential alternating allocation to starting dose of either Cohort A: 20 mg PO 3/week, q 2 weeks on a 28-day cycle, or Cohort B: 10 mg PO daily for 7 days, q 2 weeks on a 28-day cycle, for 12 cycles. Dose level -1 was cohort A: 15 mg 3/week; and cohort B: 10 mg 4/week. Patients with clinically significant cardiac diseases, bradycardia, QTc > 470 msec, bifascicular block were ineligible. EKG was performed on pre- and post-dose on day 1 & 5 of cycle 1, and pre-dose on day 1 of cycles 2-4. Relative dose intensity (RDI), a ratio of amount of drug actually delivered in mg over the amount of planned dose in mg, was calculated to evaluate the treatment feasibility as a surrogate measure. Results: The median age of the entire cohort was 60 (range, 40-73) years with a male/female = 18/12. Disease characteristics are summarized in the Table. Patients initiated pano maintenance at a median of 131 (range 91 - 178) days after autologous HCT. As of 8/1/2019, 16 patients (8 in each cohort) completed full 12 cycles of pano. The RDI for the entire cohort, cohort A, and cohort B was 94.1% (33,750mg/35,860, 98% (16,350mg/16,680mg), and 90.7% (17,400mg/19,180mg), respectively. One patient in cohort A had dose reduction, and 6 patients in cohort B had dose reductions with cytopenias (43%) and GI toxicities (43%) being the most common reasons. No patients required dose modifications due to QT prolongation thus far. There were 3 possibly treatment-associated serious adverse events (pneumonia=2; colitis=1) but all patients successfully resumed pano. Three patients progressed while on pano maintenance. No mortality has been observed thus far. Ten patients are still on pano treatment. The median follow-up is 11 (range, 1-29) months. Conclusions: RDI is 90% overall and panobinostat as a single oral maintenance agent either at 20 mg three times per week or 10 mg po daily for 7 days on alternating weeks appears to be overall well tolerated. There were more dose reductions required in the 10 mg starting dose (cohort B). Panobinostat is a safe alternative for maintenance therapy after autologous HCT. Longer follow-up is needed to confirm the utility of this approach and updated results will be presented at the meeting. Disclosures Nishihori: Novartis: Research Funding; Karyopharm: Research Funding. Baz:Sanofi: Research Funding; Bristol-Myers Squibb: Research Funding; AbbVie: Research Funding; Merck: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding. Shain:Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy. Brayer:Janssen: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Locke:Kite: Other: Scientific Advisor; Novartis: Other: Scientific Advisor; Cellular BioMedicine Group Inc.: Consultancy. Alsina:Bristol-Myers Squibb: Research Funding; Janssen: Speakers Bureau; Amgen: Speakers Bureau. OffLabel Disclosure: Panobinostat single agent maintenance therapy after autologous hematopoietic cell transplantation for multiple myeloma

scholarly journals Patient Age and Donor HLA Matching Can Stratify Allogeneic Hematopoietic Cell Transplantation (HCT) Patients into Prognostic Groups: A Collaborative Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3341-3341
Author(s):  
Sunu Cyriac ◽  
Auro Viswabandya ◽  
Zeyad Al-Shaibani ◽  
Jeffrey H. Lipton ◽  
Rajat Kumar ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Scoring System ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
University Hospital ◽  
P Value ◽  
Cell Transplant ◽  
Hla Matching ◽  
Allogeneic Hct ◽  
Weighted Score

BACKGROUND: Allogeneic hematopoeitic cell transplant (HCT) is potentially curative for a variety of hematological diseases. It is however associated with significant morbidity and mortality. Numerous pre-transplant risk scores have been developed to predict outcomes, such as the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI). This study assesses the value of the HCT-CI and related scores on a single center population, in comparison with other potential parameters influencing outcomes. A similar methodology was later applied to a different cohort of patients' data from Oslo University Hospital, Norway. METHODS: Two experienced physicians prospectively calculated the HCT-CI score for all patients transplanted at our center. The age-adjusted HCT-CI score and the augmented HCT-CI score were calculated retrospectively. Prospective calculation was performed during the patient's pre-transplant assessment before transplant admission using a pre-prepared form. The HCT-CI/age and the augmented HCT-CI (which includes ferritin, albumin and platelet count) were calculated using additional data retrospectively collected from the electronic patient records (EPR). All other patient and transplant characteristics were retrospectively collected from the EPR. Non-Relapse Mortality (NRM) and Overall survival (OS) were calculated to assess the prognostic power of the scores. We also looked at the impact of major transplant and patient related parameters in our patient population. A similar methodology was later applied to a different cohort of patients' data from Oslo University Hospital, Norway. RESULTS: From August 2014 to April 2017, 299 patients underwent allogeneic HCT at the Princess Margaret Cancer Centre (PMCC), Toronto. A similar analysis was performed in a cohort of 455 patients from Oslo University Hospital who underwent HCT between 2012 and 2018. Comparative patient characteristics are described in Table 1. On univariate analysis, 2-year OS of the PMCC cohort was 51% (95% CI 45-56%). For the HCT-CI scores 0-2 vs ≥3, 2-year OS was 53% vs 46% respectively (p=0.29). For the HCT-CI/age scores 0-2 vs ≥3, it was 56% vs 44% respectively (p=0.03). For the augmented HCT-CI scores 0-2 vs ≥3, it was 55% vs 46% respectively (p=0.05). Among other variables, age group (<50 vs 50-64 vs ≥65, p=0.02) and donor mismatch (p=0.01) were significant for OS. However, age (HR 1.48 and 1.75 for age 50-64 and ≥65 respectively, p=0.047) and donor mismatch (HR 1.60, p=0.02) alone were also prognostically significant in the multivariate analysis as well. We then developed a weighted score that would better reflect risk groups in our population. Age <50 and full HLA matching received 0 point each, age 50-64 and any mismatch (except DQ alone) received 1 point each, while age ≥65 received 2 points. The patients were grouped into 3 groups of 0, 1 and ≥ 2 points. This new simple 3 tier score predicted OS and NRM at 2 years with better accuracy. The 2 yr OS was 62%, 53% and 38% for the 3 groups (p value =0.0004) and 2 year NRM was 24%, 34% and 43% respectively (p value=0.015) (Table 2 and Figure 1). The same scoring system was later applied to an independent cohort of allogeneic HCT patients from the Oslo HCT registry and was found to be similarly significantly predictive of OS and NRM. In the Oslo cohort, the 2 yr OS was 69%, 65% and 35% for the 3 groups according to the new weighted score (p value <0.001) and 2 year NRM was 15%, 20% and 45% respectively (p value=0.015) CONCLUSION: A simple, weighted score involving donor HLA mismatch and age predicts survival and NRM better than the HCT-CI score for patients transplanted at our center with good replicability as shown from Oslo data. Efforts should continue to strive for the development of a widely applicable pre-transplant outcome predictive scoring system. Disclosures Mattsson: Gilead: Honoraria; Therakos: Honoraria; Celgene: Honoraria. Michelis:CSL Behring: Other: Financial Support.

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