Immunosuppression medication adherence after allogeneic hematopoietic stem cell transplant: Impact of a specialized clinical pharmacy program

2021 ◽  
pp. 107815522110001
Author(s):  
Florent Charra ◽  
Michael Philippe ◽  
Chloé Herledan ◽  
Anne-Gaëlle Caffin ◽  
Virginie Larbre ◽  
...  
Keyword(s):  
Clinical Pharmacy ◽  
Hematopoietic Stem Cell Transplant ◽  
Acute Gvhd ◽  
Intervention Group ◽  
Serum Levels ◽  
Control Group ◽  
Cell Transplant ◽  
Drug Adherence ◽  
Hematopoietic Stem ◽  
Discharge Prescription

This study aims to evaluate the impact of implementing a specialized clinical pharmacy program in patients with allogeneic hematopoietic stem cell transplant (HSCT) on their adherence to the immunosuppression treatment after discharge. A prospective open interventional design using a retrospective control group was used. The intervention was based on pharmaceutical consultations: the first was performed the day before discharge of HSCT unit and the next consultations during day-care follow-up (weeks 2 and 4 after discharge). Proactive medication reconciliation was implemented with a complete list of medications before the discharge prescription. The discharge prescription summarized on a personalized drug schedule was explained to the patient. The importance of optimal adherence and the potential problems related to self-medication were explained to the patient. Immunosuppression drug adherence was assessed by a direct method using serum levels of calcineurin inhibitors. The potential impact on acute GvHD, and infection was investigated. Twenty-six patients were included in the specialized clinical pharmacy program and 35 patients were in the control group. Seventy-nine pharmaceutical consultations were conducted in the intervention group, lasting a mean 25 min and 16 min for the first and following consultations, respectively. Serum levels in the therapeutic target range were higher in the intervention group (61.5% versus 53.0%, p = 0.07), with greater intra-individual variation (p = 0.005). There was no significant intergroup difference in acute GvHD (53.8% versus 50.3%, p = 0.85) or infection (26.9 versus 22.8%, p = 0.72). The implementation of a specialized clinical pharmacy program for patients who have received allogeneic HSCT seems to be beneficial for immunosuppression drug adherence; this now needs to be confirmed in a multicenter study involving a larger number of patients.

Cytomegalovirus (CMV) gB3 Genotype Is Associated with Acute Gvhd and CMV Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients (HSCT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1958-1958
Author(s):  
Débora de Campos Dieamant ◽  
Sandra Helena Alves Bonon ◽  
Francisco J P Aranha ◽  
Gislaine O. Duarte ◽  
Virginio C.O. Fernandes ◽  
...  
Keyword(s):  
Viral Load ◽  
Hematopoietic Stem Cell Transplant ◽  
Acute Gvhd ◽  
Gastrointestinal Disease ◽  
Antiviral Treatment ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Grade Ii ◽  
Cmv Disease

Abstract Abstract 1958 Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). Objectives: The goals of this study were: identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with the CMV disease, acute GVHD and overall survival. Study design: The diagnosis of active CMV infection after allogeneic HSCT was detected by Antigenemia (AGM) and/or Nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using the N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment. Results: Were evaluated 63 allogeneic HSCT recipients, 49/63 patients (78%) presented active CMV infection detected by AGM and/or N-PCR, in a median time of 38 days after the transplant. The distribution of CMV gB genotypes in these 49 patients with active CMV infection was as follow: gB1, 19/49 (38.8%); gB2, 17/49 (34.7%); gB3, 3/49 (6.1%); gB4, 7/49 (14.3%) and three patients (6.1%) had mixed infection with gB1+gB3, gB1+gB4 and gB2+gB4. Acute GVHD grade II-IV occurred in 17/49 (34.7%) patients: 8/19 (gB1-42%), 1/17 (gB2 - 5.9%), 4/4 (gB3 - 100%) and 4/9 (gB4 - 44.4%). The distribution of the frequency of acute GVHD grade II-IV between the genotypes was statistically different (p=0.008). CMV disease occurred in 3/49 (6.1%) patients, characterized for gastrointestinal disease and these three patients had infection with CMV gB3 genotype. This genotype of CMV was also associated with higher viral load during antiviral treatment and worse survival. Conclusions: This study demonstrated that the frequency of active CMV infection in HSCT population was high (78%). The most prevalent genotype in patients with active CMV infection was gB1 and gB3 genotype was associated with acute GVHD grade II-IV, CMV gastrointestinal disease, higher viral load during antiviral treatment and worse survival. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Role of IgM-Enriched Immunoglobulin (Pentaglobin) in Septic Patients with Hematological Disease

2021 ◽  
Author(s):  
Pedro Amoedo Fernandes ◽  
Flavia Tobaldini Russo ◽  
Lucas Augusto Monetta da Silva ◽  
Lafayete Willian Ferreira Ramos ◽  
Aline de Almeida Simões ◽  
...  
Keyword(s):  
Septic Shock ◽  
Intervention Group ◽  
Serum Levels ◽  
Control Group ◽  
Hematological Disease ◽  
Hematopoietic Stem ◽  
Humoral Immunodeficiency ◽  
Group A ◽  
Low Serum

Background: Patients with hematological disease are 15 times more likely to develop sepsis than the general population. The patient with hematological disease and, mainly, those undergoing hematopoietic stem cell transplantation (HSCT), develop a severe secondary humoral immunodeficiency, with low serum levels of IgM, which may take more than a year to be restored. Materials and Methods: This is a retrospective, controlled and observational study that analyzed 51 patients with underlying hematological disease, who were diagnosed with sepsis or septic shock during the study period, to evaluate whether IgM-rich Ig replacement decreases the 30-day mortality. Results: Of the 51 patients, 35 patients received IgM-rich immunoglobulin (group A) and 16 (31%) received conventional therapy. Eleven (69%) patients in the control group were alive after 30 days compared to 11 (34%) patients in the intervention group, p= 0.013. Conclusion: There are no apparent benefits in the use of IgM-rich immunoglobulin in septic patients with hematological disease.

scholarly journals Impact of Natural Killer Cells Reconstitution on Outcomes after Allogenic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4880-4880
Author(s):  
Moazzam Shahzad ◽  
Amna Y Shah ◽  
Muhammad Usman Zafar ◽  
Ezza Tariq ◽  
Anam Hamid ◽  
...  
Keyword(s):  
Stem Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Hematopoietic Stem Cell ◽  
Research Funding ◽  
Hematopoietic Stem Cell Transplant ◽  
Acute Gvhd ◽  
Meta Analysis ◽  
Cell Transplant ◽  
Hematopoietic Stem

Abstract Background: Natural killer (NK) cells are the first cells to recover following allogeneic hematopoietic stem cell transplant (HSCT) and play a crucial role in enabling engraftment, preventing post-transplant infection and tumor relapse. In addition, NK cells also reduce the risk of graft versus host disease (GvHD) and increase the graft versus leukemia effect (GVL). The purpose of this systematic review and meta-analysis is to know the impact of NK cells reconstitution on outcomes of allogeneic HSCT. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search was conducted on PubMed, Cochrane Library, and ClinicalTrials.gov through January 2021. We used MeSH terms and keywords for "hematologic malignancies" OR "hematopoietic stem cell transplantation" AND "natural killer cells." No filters or publication time limits were applied for the search. A total of 13 studies were included after screening 988 records and excluding duplicates, review, and non-relevant articles. An arbitrary value of NK cell count of 22.2 cell/ul was set as a cut-off to divide between high and low groups of NK where applicable. Quality evaluation was done using the NIH quality assessment tool and Inter-study variance was calculated using Der Simonian-Laird Estimator. Pooled analysis was done using the 'meta' package (Schwarzer et al. R programming language), and proportions with 95% confidence intervals (CI) were computed. Results: A total of 1623 patients were evaluated from 13 studies. (Table 1) The median age of patients was 44 (8.6-63) years and 33.5% were males. The median duration of follow-up was 18 (0.3-122) months. The median 2-year overall survival (OS) for high NK cohort and low NK cohort was 77% (95%CI 0.70-0.83, I 2 =82%, n=982) and 52%(95%CI 0.38-0.67, I 2 =95%, n=982), respectively. The pooled rate of relapse in high NK group was 8% (95%CI 0.01-0.19, I 2 =83%, n=226) and it was 20% (95%CI 0.06-0.39, I 2 =90%, n=226) for low NK group. The pooled incidence of acute GvHD was 24% (95%CI 0.09-0.42, I 2 =91%, n=336) and 44% (95%CI 0.26-0.62, I 2 =91%, n=336) for high and low NK cohorts, respectively. The pooled incidence for viral infection for high NK group was 17% (95%CI 0.01-0.47, I 2 =98%, n=508) while it was 29% (95%CI 0.04-0.65, I 2 =98%, n=508) for low NK group, respectively. Conclusion: Higher reconstitution of NK cells after allogeneic hematopoietic stem cell transplant has a favorable impact on outcomes, including better overall survival and low incidence of relapse, acute GvHD, and viral infections. Our findings suggest the need for further prospective studies to investigate utility of NK cells infusion early post-transplant to improve clinical outcomes and survival. Figure 1 Figure 1. Disclosures McGuirk: Bellicum Pharmaceuticals: Research Funding; Novartis: Research Funding; EcoR1 Capital: Consultancy; Astelllas Pharma: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding; Gamida Cell: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Pluristem Therapeutics: Research Funding.

Caphosol Mouth Rinse Diminishes Oral Mucositis In Allo-HSCT Recipients.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3498-3498 ◽  
Author(s):  
Miroslaw Markiewicz ◽  
Dzierzak Mietla Monika ◽  
Patrycja Zielinska ◽  
Tomasz Kruzel ◽  
Tomasz Czerw ◽  
...  
Keyword(s):  
Oral Mucositis ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Control Group ◽  
Cell Transplant ◽  
Mouth Rinse ◽  
Oral Toxicity ◽  
Hematopoietic Stem ◽  
Conditioning Treatment ◽  
Swallowing Problems

Abstract Abstract 3498 Introduction: Oral mucositis is a complication of conditioning treatment that produces pain and morbidity in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. The rationale of this study was to evaluate the efficacy of a calcium phosphate mouth rinse (Caphosol) vs standard regimen in 40 adult patients undergoing allo-HSCT. Patients and Methods: 40 patients treated with allo-HSCT (31 from unrelated donors, 9 from siblings) performed in Hematology and BMT center in Katowice in 2009 were randomized and stratified by the conditioning regimen (busulfan-, treosulfan- or TBI- based), type of transplant (unrelated or related) and age into two equal groups. Treatment group received Caphosol washes 4 times daily from first day of conditioning until reaching ANC 0.2 G/l. Control group received standard topical mouth care with salvia, antibacterial and antifungal solutions. During the trial patients subjectively assessed level of pain in mouth and in pharynx using 0–10 scale and swallowing problems using 0–5 scale. Mucositis was judged by experienced physician. Nonparametric Mann-Whitney U-tests were used for statistical analysis. Results: Average oral toxicity in WHO scale in Caphosol vs control group was 0.9 vs 1.8 (p=0.02), duration of mucositis was 3.2 vs 7.1 days (p=0.02). Total parenteral nutrition (TPN) due to mucosits was required in Caphosol vs control group in 0 vs 6 pts, average duration of TPN was 0 vs 1.9 days (p=0.009). Analgetics were required, respectively, in 3 vs 9 pts and analgesy lasted for 1.1 vs 3.4 days (p=0.047). Average subjective peak pain in mouth was 0.85 vs 1.75 (p=0.005) and in pharynx 1.95 vs 2.2 (NS) in Caphosol vs control group, average pain intensity was lower in Caphosol group throughout the whole period of mucositis. Intensity of swallowing problems tended to be lower in Caphosol group (NS). Acute GVHD was observed in 7 vs 9 pts in Caphosol vs control group and its average degree was 0.5 vs 0.9 (NS). Conclusions: Caphosol mouth rinse in the allo-HSCT recipients is associated with decrease of oral toxicity, lower peak pain due to mucositis and its shorter duration. In consequence, comfort of life is improved and the incidence of acute GVHD is reduced, as well as the requirement of TPN and analgetics. Disclosures: No relevant conflicts of interest to declare.

Impact of Vitamin D Level After Allogeneic Hematopoietic Stem Cell Transplant

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1954-1954
Author(s):  
Lisa Sproat ◽  
Jane Olsen ◽  
Kristen Beebe ◽  
Rochelle Chiffelle ◽  
Susan Gerber ◽  
...  
Keyword(s):  
Vitamin D ◽  
Stem Cell ◽  
Survival Analysis ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Acute Gvhd ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Risk Of Mortality

Abstract Abstract 1954 Introduction: Vitamin D (VD) deficiency can cause osteomalacia, aching bone pain, muscle weakness, fatigue, increase risk of fracture and precipitate or exacerbate osteopenia/osteoporosis. Allogeneic hematopoietic stem cell transplant (HCT) patients are susceptible to low VD level secondary to poor oral intake, decreased exposure to sunlight and treatment related malabsorption. VD level has been correlated to cancer incidence and VD metabolites have been used in the treatment of myeloid leukemia. VD shows promising immunomodulatory properties and correction of low VD level may mitigate manifestations of graft versus host disease (GVHD). Reports have suggested that low VD level appears to increase the incidence of GVHD. We hypothesize that there is a relationship between low VD level and morbidity (specifically incidence of acute GVHD), mortality and relapse incidence after HCT. We therefore studied VD levels pre- and post-HCT to determine if VD level impacts these outcomes. Patients and Methods: 241 patients underwent myeloblative or non-myeloablative HCT between January 1, 2009 and January 31, 2011 at our institution. Baseline demographic data, disease characteristics, transplant variables and outcomes data were obtained from the transplant database. These data were supplemented by retrospective chart review for pre- and post-transplant VD level. Categories for VD level included normal (>30 ng/ml) or abnormal (<30 ng/ml). Results: 131 (54%) of patients who underwent myeloblative or non-myeloablative HCT had their VD level evaluated either pre-transplant, post-transplant or both. Pre-HCT 57 (56%) patients, 100 days post-HCT 55 (59%) patients and 365 days post-HCT 12 (32%) patients had a low VD level. 51 (38%) of patients had a reduced intensity HCT and 80 patients (62%) had an ablative conditioning regimen. 11 (8.4%) patients had acute GVHD. Comparison of VD level among those with acute GVHD did show a higher incidence of acute GVHD between those with a low or normal VD level (HR=3.14, 95% CI: 0.35–28.33) however this association was not statistically significant (p=0.3079). Survival analysis in those with a low VD level pre-HCT showed there was not a higher risk of mortality (HR=1.14, 95% CI: 0.18–7.38) after adjusting for post- VD level, and this association was not statistically significant (p=0.8921). Survival analysis in those with a low VD level post-HCT did show a higher risk of mortality (HR=2.59, 95% CI: 0.26–25) after adjusting for pre-HCT VD level, however, this association was not statistically significant (p=0.4155). The relationship between VD level and relapse at 1 year post-HCT was not able to be examined because the VD level for patients who relapsed was not available. Conclusions: Half of patients undergoing HCT had VD testing pre- or post- HCT. Just over half of the patients tested had a low VD level pre- and 100 days post-HCT. It is notable that 365 days post HCT the number of patients with low VD level had decreased. This could be attributable to less time in the hospital thus increasing sun exposure, increasing performance status allowing better ingestion and absorption of VD in the gastrointestinal tract or proper supplementation of a low level noted previously. There was no significant difference in incidence of acute GVHD by VD level though there was a trend for increased risk. Pre- and post-HCT VD level did not significantly impact mortality but there was a trend toward higher risk in those with a low VD level post-HCT. This is the first study, to our knowledge, to evaluate the impact of VD level on mortality post-HCT. Our study confirms that many patients have a low VD level pre-and post-HCT. These findings, especially the trend towards a higher mortality risk and higher incidence of acute GVHD in those who have a low VD level post-HCT, warrant further prospective investigation. VD supplementation may be a low cost, easy to implement addition to routine post HCT care that might reduce HCT associated mortality. Disclosures: Reeder: Celgene: Research Funding.

Long-term follow-up of adult hematopoietic stem cell transplant recipients diagnosed with COVID-19.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19028-e19028
Author(s):  
Stephanie Hoffman ◽  
Pavan Reddy ◽  
John Martin Magenau ◽  
Attaphol Pawarode ◽  
Brian Parkin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Acute Gvhd ◽  
Stem Cell Transplant ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Long Term Follow Up

e19028 Background: Long-term complications of COVID-19 in hematopoietic stem cell transplant (HCT) recipients are unknown. Recent studies have described short term outcomes of COVID-19 infection post allogeneic (allo) and autologous (auto) HCT. In this study we provide long term follow-up of the outcomes of COVID-19 infection in allo and auto HCT recipients. Methods: We performed a retrospective study of adult patients who have received allo or auto HCT and were subsequently diagnosed with COVID-19 infection between March-December 2020. We summarized patient characteristics, laboratory and treatment data related to COVID-19 infection in these patients. Results: In this study, we provide long-term follow-up of over 7 months. Fifteen patients were identified for inclusion (allo n = 12, auto n = 3). Median follow-up was 7.8 months (range 1.9-10.7) for surviving patients. Median age at COVID-19 diagnosis was 55 years (range 24-77). Most patients were > 1 year out from transplant (allo n = 10, auto n = 1, 73%). Two patients (allo n = 1, auto n = 1, 13%) had undergone transplant within the preceding month. Most allo patients (n = 11, 73%) had received myeloablative conditioning. At the time of COVID-19 diagnosis, 9 allo patients (75%) were on immunosuppression (IS) (n = 7 for chronic graft-versus-host-disease (GVHD); n = 2 for GVHD prophylaxis). Eleven patients (73%) required hospitalization (allo n = 9, auto n = 2). Per the National Institutes of Health definitions of COVID-19 illness severity, 3 patients had critical disease (allo n = 2, auto n = 1, 20%), 5 severe (allo n = 5, 33%), 3 moderate (allo n = 2, auto n = 1, 20%), and 4 mild (allo n = 3, auto n = 1, 27%). All patients with chronic GVHD required hospitalization. Two patients died (allo n = 1, auto n = 1, 13%)—both had critical COVID-19 infections, were > 65 years old, > 3 years out from transplant, and had significant comorbidities. The allo patient was receiving prednisone < 1 mg/kg for chronic lung GVHD at COVID-19 diagnosis. Two allo patients developed either acute GVHD or chronic GVHD exacerbation within 3 months of their infection. One patient developed biopsy-proven acute GVHD (max grade III) 3 weeks after her infection and another patient developed a severe exacerbation of chronic GVHD within 3 months—both continue to require multi-modal IS. The remaining 7 patients with chronic GVHD have been maintained on either stable or tapered IS. Conclusions: Given the effect of COVID-19 infection, its impact on HCT recipients is important to define. The majority of HCT patients who contracted moderate-critical COVID-19 infections in our study were either on IS or had significant comorbidities. Our observational data points to the importance of long-term follow-up in HCT patients. Future studies are needed to delineate whether there is a relationship between COVID-19 infection and GVHD development or exacerbation. The role of vaccination in HCT recipients remains to be explored.

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