scholarly journals Safety and reactogenicity of the recombinant zoster vaccine after allogeneic hematopoietic cell transplantation

2021 ◽  
Vol 5 (6) ◽  
pp. 1585-1593
Author(s):  
Emily Baumrin ◽  
Natalie E. Izaguirre ◽  
Bruce Bausk ◽  
Monica M. Feeley ◽  
Camden P. Bay ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Zoster Vaccine ◽  
Varicella Zoster ◽  
Increased Risk ◽  
Adjusted Incidence Rate ◽  
Recombinant Zoster Vaccine ◽  
Grade 3

Abstract Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. A nonlive adjuvanted recombinant zoster vaccine (RZV) has been developed to prevent herpes zoster (HZ), but there are no recommendations for use in this population. In this single-center prospective observational cohort study, we assessed the safety and reactogenicity of RZV, as well as incidence of graft-versus-host disease (GVHD) and confirmed cases of HZ after vaccination. Between December of 2018 and June of 2020, patients aged ≥18 years received 2 doses of RZV between 9 and 24 months after HCT, with the doses separated by ≥8 weeks. One hundred and fifty-eight patients (mean age, 55 years; 42% women) received ≥1 dose (total vaccinated cohort), and 150 patients (95%) received 2 doses (modified total vaccinated cohort). Solicited reactions occurred in 92.1% of patients (grade 3, 32.5%), owing mostly to injection site pain, which occurred in 86% (grade 3, 16%). The cumulative incidence of GVHD in the peri-vaccination period was no different than in historical controls (adjusted incidence rate ratio, 1.05; 95% confidence interval, 0.8-1.38). There were 4 cases of HZ in the total vaccinated cohort (2.5%) and 3 cases in the modified total vaccinated cohort (28.3/1000 person-years). Among recipients of allogeneic HCT, RZV was safe, tolerable, and did not increase rates of GVHD. Future clinical trials are needed to determine the immunogenicity and efficacy of RZV in this population.

scholarly journals Causes and Effects of Methotrexate Dose Alterations in Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2460-2460 ◽  
Author(s):  
Radha Ramanan ◽  
Andrew Boon Ming Lim ◽  
Kate Mason ◽  
Jeffrey Szer ◽  
David Ritchie
Keyword(s):  
Overall Survival ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
World Health ◽  
Gvhd Prophylaxis ◽  
Increased Risk ◽  
Grade 3

Abstract Aim To identify the causes and consequences of omission and/or reduction of methotrexate (MTX) doses in graft-versus-host disease (GVHD) prophylaxis used during allogeneic hematopoietic cell transplantation (alloHCT). Method We conducted a retrospective medical record review of 125 alloHCTs performed between the years 2011 and 2013 at our hospital where MTX (15, 10, 10, 10 mg/m2 intravenously on day [D] +1, D+3, D+6, D+11 respectively) is used with cyclosporine as GVHD prophylaxis. The association of MTX dose omission with overall survival (OS), non-relapse mortality (NRM) and acute GVHD, measured from a landmark of D+12, was evaluated with univariate and multivariate analysis. Results 116 patients (median age 48, range 17-67, 59% male) were eligible for analysis. Commonest indications for alloHCT were acute leukemia (47%) and chronic lymphoproliferative disorders (28%). Conditioning was myeloablative in 54%, donors were siblings in 53%, and grafts were peripheral blood in 87%. 85 patients (73%) received all four full doses of MTX. 22 patients had a dose omission at D+11, and two at both D+6 and D+11. 43 patients were given folinic acid rescue. Documented reasons for MTX alteration were mucositis (n = 22; World Health Organisation mucositis grade 4 in 16 patients, grade 3 in 4 patients and grade 2 in 2 patients), fluid overload (n = 10), liver impairment (n = 8, median bilirubin 83 micromol/L, range 19-204 micromol/L, normal < 21 micromol/L), renal impairment (n = 8, median creatinine 138 micromol/L, range 67-276 micromol/L, normal 45-90 micromol/L) and sepsis (1). MTX omission was associated with poorer OS (48% vs 90%; hazard ratio [HR] for mortality 5.4, 95% CI 2.5-11.7, P < 0.001, Figure 1) and higher NRM (39% vs 5%, HR 10.2, 95% CI 3.4-30.8, P < 0.001, Figure 2) at 12 months post landmark. A pattern of ongoing NRM was observed beyond day 100. Strikingly, those patients who received all four full doses of MTX had NRM of 0% at 100 days post landmark. There was no difference in rates of grade 2-4 (24% vs 22%, P = .950) or grade 3-4 (9% vs 11%, P = .662) acute GVHD, or relapse (20% vs 17%, P = .514), at day 100 post landmark. Conclusion MTX dose reduction has no significant impact on GVHD development, suggesting that MTX omissions or other adjustments of GVHD prophylaxis did not lead to enhanced T cell activation. However, it seems that the need to reduce MTX indicates an increased risk of NRM, likely reflecting ongoing organ dysfunction. Older patients or those with pre-transplant co-morbidities may be better served by strategies that lower the likelihood of organ toxicity, including reduced intensity conditioning and lower initial doses of MTX. Figure 1. Overall survival according to whether or not any methotrexate (MTX) was omitted. Figure 1. Overall survival according to whether or not any methotrexate (MTX) was omitted. Figure 2. Non-relapse mortality according to whether or not any methotrexate (MTX) was omitted. Figure 2. Non-relapse mortality according to whether or not any methotrexate (MTX) was omitted. Disclosures No relevant conflicts of interest to declare.

scholarly journals Recipient and donor genetic variants associated with mortality after allogeneic hematopoietic cell transplantation

2020 ◽  
Vol 4 (14) ◽  
pp. 3224-3233
Author(s):  
Paul J. Martin ◽  
David M. Levine ◽  
Barry E. Storer ◽  
Sarah C. Nelson ◽  
Xinyuan Dong ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Genetic Variants ◽  
Hematopoietic Cell Transplantation ◽  
Genome Wide Association Study ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
European Ancestry ◽  
A Genome ◽  
Grade 3 ◽  
Highly Correlated

Abstract Many studies have suggested that genetic variants in donors and recipients are associated with survival-related outcomes after allogeneic hematopoietic cell transplantation (HCT), but these results have not been confirmed. Therefore, the utility of testing genetic variants in donors and recipients for risk stratification or understanding mechanisms leading to mortality after HCT has not been established. We tested 122 recipient and donor candidate variants for association with nonrelapse mortality (NRM) and relapse mortality (RM) in a cohort of 2560 HCT recipients of European ancestry with related or unrelated donors. Associations discovered in this cohort were tested for replication in a separate cohort of 1710 HCT recipients. We found that the donor rs1051792 A allele in MICA was associated with a lower risk of NRM. Donor and recipient rs1051792 genotypes were highly correlated, making it statistically impossible to determine whether the donor or recipient genotype accounted for the association. Risks of grade 3 to 4 graft-versus-host disease (GVHD) and NRM in patients with grades 3 to 4 GVHD were lower with donor MICA-129Met but not with MICA-129Val, implicating MICA-129Met in the donor as an explanation for the decreased risk of NRM after HCT. Our analysis of candidate variants did not show any other association with NRM or RM. A genome-wide association study did not identify any other variants associated with NRM or RM.

scholarly journals Spontaneous fertility in a male thalassemic patient after allogeneic hematopoietic cell transplantation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Nicoletta Iacovidou ◽  
Maria Kollia ◽  
Emmeleia Nana ◽  
Theodora Boutsikou ◽  
Christos Savvidis ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Semen Analysis ◽  
Conditioning Regimen ◽  
Thalassemia Major ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Thalassemic Patient ◽  
Increased Risk ◽  
Long Term Treatment

Patients with thalassemia major who received allogeneic hematopoietic cell transplantation are at increased risk of gonadal insufficiency and reduced fertility due to the toxicity of both the transfusional iron overload and the gonadotoxic effects of drugs used in the conditioning regimen. We present a case of an ex-thalassemic patient with spontaneous recovery of spermatogenesis that fathered a healthy, term male neonate. Maternal hemoglobin electrophoresis was within normal limits. At the age of 9.5 years the patient underwent hematopoietic cell transplantation. The conditioning therapy included busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg). No irradiation was administered. Thirty-two days after the hematopoietic cell transplantation the patient developed acute graft-versus-host disease needing long-term treatment with methylprednisolone, cyclosporine and immunoglobulin. Although consecutive semen analyses after the hematopoietic cell transplantation revealed azoospermia, the last semen analysis before conception, at the age of 33 years, was improved and normal follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (Te) levels were detected. The current pregnancy was the result of physical conception. In this case, it seems that thalassemia major along with the respective treatment prior to- and posthematopoietic cell transplantation did not irreparably impair spermatogenesis, probably due to the pre-pubertal time frame they were implemented. 对于接受异基因造血细胞移植的重型地中海贫血患者，由于输注性铁过载的毒性和预处理方案中所用药物性腺毒性作用这两方面的原因，都使其面临更大的性腺功能不全风险和更低的生育力。本文报道一例精子发生出现自然恢复的原重型地中海贫血患者，他成功孕育出一个健康的足月男婴。母体血红蛋白电泳在正常范围内。患者在9岁半时接受了造血细胞移植。预处理治疗包括白消安（16 mg/kg）和环磷酰胺（200 mg/kg）。未给予照射。造血细胞移植32天后，患者出现急性移植物抗宿主病，需要长期使用甲基强的松龙、环孢素和免疫球蛋白治疗。虽然造血细胞移植后连续的精液分析显示无精子症，但在33岁时受精前的最后一次精液分析有所改善，经检测发现卵泡刺激素（FSH）、黄体生成素（LH）和睾酮（Te）水平正常。目前的怀孕是自然受孕的结果。在这个病例中，看来重型地中海贫血以及造血细胞移植前后相应的治疗并没有对精子发生造成不可恢复的破坏，这可能是由于移植时处于青春发育期前时间段的原因。

scholarly journals CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation

Blood ◽  
2009 ◽  
Vol 113 (7) ◽  
pp. 1581-1588 ◽  
Author(s):  
Asad Bashey ◽  
Bridget Medina ◽  
Sue Corringham ◽  
Mildred Pasek ◽  
Ewa Carrier ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Single Infusion ◽  
Graft Versus Host ◽  
Mantle Cell ◽  
Organ Specific ◽  
Grade 3 ◽  
Dose Limiting Toxicity

Abstract Relapse of malignancy after allogeneic hematopoietic cell transplantation (allo-HCT) remains a therapeutic challenge. Blockade of the CTLA4 molecule can effectively augment antitumor immunity mediated by autologous effector T cells. We have assessed the safety and preliminary efficacy of a neutralizing, human anti-CTLA4 monoclonal antibody, ipilimumab, in stimulating the graft-versus-malignancy (GVM) effect after allo-HCT. Twenty-nine patients with malignancies that were recurrent or progressive after allo-HCT, received ipilimumab as a single infusion at dose cohorts between 0.1 and 3.0 mg/kg. Dose-limiting toxicity was not encountered, and ipilimumab did not induce graft-versus-host disease (GVHD) or graft rejection. Organ-specific immune adverse events (IAE) were seen in 4 patients (grade 3 arthritis, grade 2 hyperthyroidism, recurrent grade 4 pneumonitis). Three patients with lymphoid malignancy developed objective disease responses following ipilimumab: complete remission (CR) in 2 patients with Hodgkin disease and partial remission (PR) in a patient with refractory mantle cell lymphoma. At the 3.0 mg/kg dose, active serum concentrations of ipilimumab were maintained for more than 30 days after a single infusion. Ipilimumab, as administered in this clinical trial, does not induce or exacerbate clinical GVHD, but may cause organ-specific IAE and regression of malignancy. This study is registered at http://clinicaltrials.gov under NCI protocol ID P6082.

scholarly journals Increased risk of breast cancer among survivors of allogeneic hematopoietic cell transplantation: a report from the FHCRC and the EBMT-Late Effect Working Party

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 939-944 ◽  
Author(s):  
Debra L. Friedman ◽  
Alicia Rovo ◽  
Wendy Leisenring ◽  
Anna Locasciulli ◽  
Mary E. D. Flowers ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Proportional Hazards Model ◽  
Multivariable Analysis ◽  
Working Party ◽  
Cox Proportional Hazards Model ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Increased Risk

As risk for secondary breast cancer is elevated among cancer survivors treated with conventional therapy, we sought to determine the risk among 3337 female 5-year survivors who underwent an allogeneic hematopoietic cell transplantation (HCT) at the Fred Hutchinson Cancer Research Center or at one of 82 centers reporting to the European Bone Marrow Transplant Registry. Risk was calculated using standardized incidence ratios (SIRs), and risk factors were evaluated with a multivariable Cox proportional hazards model. Fifty-two survivors developed breast cancer at a median of 12.5 (range: 5.7-24.8) years following HCT (SIR = 2.2). Twenty-five–year cumulative incidence was 11.0%, higher among survivors who received total body irradiation (TBI) (17%) than those who did not receive TBI (3%). In multivariable analysis, increased risk was associated with longer time since transplantation (hazard ratio [HR] for 20+ years after transplantation = 10.8), use of TBI (HR = 4.0), and younger age at transplantation (HR = 9.5 for HCT < 18 years). Hazard for death associated with breast cancer was 2.5 (95% CI: 1.1-5.8). We conclude that female survivors of allogeneic HCT are at increased risk of breast cancer and should be educated about the need for regular screening.

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.

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