Dual cytokine blockade in acute GVHD

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.

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Impact of HLA Disparity on the Risk of Overall Mortality in Patients Who Developed Grade II-IV Acute GVHD

Transplantation and Cellular Therapy ◽

10.1016/s2666-6367(21)00328-6 ◽

2021 ◽

Vol 27 (3) ◽

pp. S260

Author(s):

Shigeo Fuji ◽

Akitoshi Hakoda ◽

Junya Kanda ◽

Makoto Murata ◽

Seitaro Terakura ◽

...

Keyword(s):

Acute Gvhd ◽

Grade Ii ◽

Overall Mortality

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Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantation

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001818 ◽

2021 ◽

Vol 9 (2) ◽

pp. e001818 ◽

Cited By ~ 1

Author(s):

Chantal Saberian ◽

Noha Abdel-Wahab ◽

Ala Abudayyeh ◽

Hind Rafei ◽

Jacinth Joseph ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Myelodysplastic Syndromes ◽

Myeloid Leukemia ◽

Acute Gvhd ◽

Checkpoint Inhibitors ◽

Post Transplantation ◽

Hematopoietic Stem ◽

Gvhd Prophylaxis ◽

Acute Myeloid

BackgroundImmune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD). We analyzed the association between GVHD prophylaxis and frequency of GVHD in patients who had received ICI therapy after alloHCT.MethodsA retrospective study was performed in 21 patients with acute myeloid leukemia (n=16) or myelodysplastic syndromes (n=5) who were treated with antiprogrammed cell death protein 1 (16 patients) or anticytotoxic T lymphocyte-associated antigen 4 (5 patients) therapy for disease relapse after alloHCT. Associations between the type of GVHD prophylaxis and incidence of GVHD were analyzed.ResultsFour patients (19%) developed acute GVHD. The incidence of acute GVHD was associated only with the type of post-transplantation GVHD prophylaxis; none of the other variables included (stem cell source, donor type, age at alloHCT, conditioning regimen and prior history of GVHD) were associated with the frequency of acute GVHD. Twelve patients received post-transplantation cyclophosphamide (PTCy) for GVHD prophylaxis. Patients who received PTCy had a significantly shorter median time to initiation of ICI therapy after alloHCT compared with patients who did not receive PTCy (median 5.1 months compared with 26.6 months). Despite early ICI therapy initiation, patients who received PTCy had a lower observed cumulative incidence of grades 2–4 acute GVHD compared with patients who did not receive PTCy (16% compared with 22%; p=0.7). After controlling for comorbidities and time from alloHCT to ICI therapy initiation, the analysis showed that PTCy was associated with a 90% reduced risk of acute GVHD (HR 0.1, 95% CI 0.02 to 0.6, p=0.01).ConclusionsICI therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after alloHCT may be a safe and feasible option. PTCy appears to decrease the incidence of acute GVHD in this cohort of patients.

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Mesenchymal stromal cells as prophylaxis for graft-versus-host disease in haplo-identical hematopoietic stem cell transplantation recipients with severe aplastic anemia?—a systematic review and meta-analysis

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02170-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ruonan Li ◽

Jingke Tu ◽

Jingyu Zhao ◽

Hong Pan ◽

Liwei Fang ◽

...

Keyword(s):

Systematic Review ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Stromal Cells ◽

Acute Gvhd ◽

Meta Analysis ◽

Cmv Infection ◽

Hematopoietic Stem ◽

Graft Versus Host

Abstract Background Mesenchymal stromal cells (MSCs) are an emerging prophylaxis option for graft-versus-host disease (GVHD) in haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) recipients with severe aplastic anemia (SAA), but studies have reported inconsistent results. This systematic review and meta-analysis evaluates the efficacy of MSCs as prophylaxis for GVHD in SAA patients with haplo-HSCT. Methods Studies were retrieved from PubMed, EMBASE, Cochrane, Web of Science, and http://clinicaltrials.gov from establishment to February 2020. Twenty-nine single-arm studies (n = 1456) were included, in which eight (n = 241) studies combined with MSCs and eleven (n = 1215) reports without MSCs in haplo-HSCT for SAA patients. The primary outcomes were the incidences of GVHD. Other outcomes included 2-year overall survival (OS) and the incidence of cytomegalovirus (CMV) infection. Odds ratios (ORs) were calculated to compare the results pooled through random or fixed effects models. Results Between MSCs and no MSCs groups, no significant differences were found in the pooled incidences of acute GVHD (56.0%, 95% CI 48.6–63.5% vs. 47.2%, 95% CI 29.0–65.4%; OR 1.43, 95% CI 0.91–2.25; p = 0.123), grade II–IV acute GVHD (29.8%, 95% CI 24.1–35.5% vs. 30.6%, 95% CI 26.6–34.6%; OR 0.97, 95% CI 0.70–1.32; p = 0.889), and chronic GVHD (25.4%, 95% CI 19.8–31.0% vs. 30.0%, 95% CI 23.3–36.6%; OR 0.79, 95% CI 0.56–1.11; p = 0.187). Furtherly, there was no obvious difference in 2-year OS (OR 0.98, 95% CI 0.60–1.61; p = 1.000) and incidence of CMV infection (OR 0.61, 95% CI 0.40–1.92; p = 0.018). Conclusions Our meta-analysis indicates that the prophylactic use of MSC co-transplantation is not an effective option for SAA patients undergoing haplo-HSCT. Hence, the general co-transplantation of MSCs for SAA haplo-HSCT recipients may lack evidence-based practice.

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