Transplantation – Hematopoietic
ATS Guidelines on Invasive Pulmonary Aspergillosis and Antifungal Strategies in Critically Ill Adults
7 Jan, 2025 | 12:29h | UTCIntroduction: This summary provides an overview of a recent American Thoracic Society clinical practice guideline addressing two core questions in adult pulmonary and critical care practice. First, it examines whether combination therapy with a mold-active triazole (most data concern voriconazole, though newer agents such as isavuconazole or posaconazole may also be considered) plus an echinocandin (specifically caspofungin, micafungin, or anidulafungin) offers added benefit over mold-active triazole monotherapy for patients with proven or probable invasive pulmonary aspergillosis (IPA). Second, it evaluates whether routine use of prophylactic or empiric antifungal agents against Candida species is advisable in critically ill, nonneutropenic, nontransplant patients at risk of invasive candidiasis (IC). By synthesizing available evidence using the GRADE approach, this guideline aims to support clinicians in optimizing therapeutic strategies and improving patient outcomes in these complex infections.
Key Recommendations:
Initial Combination Therapy vs. Monotherapy for IPA
- For patients with proven or probable IPA, the guideline makes a conditional recommendation, meaning the best choice isn’t entirely clear. Both initial combination therapy (mold-active triazole + echinocandin) and monotherapy (mold-active triazole alone) are considered reasonable options.
- Evidence stems primarily from studies in hematologic malignancy (HM) or hematopoietic stem cell transplant (HSCT) recipients, with mixed findings in observational cohorts and a key randomized trial favoring combination therapy, particularly in a subgroup diagnosed by positive galactomannan assays.
- When critical illness or triazole resistance is a concern, combination therapy may be considered, but there is insufficient evidence to categorically endorse one approach over the other.
Prophylactic or Empiric Antifungal Therapy for Candida in Critically Ill Patients
- In nonneutropenic, nontransplant adult ICU patients at risk for IC, the guideline makes a conditional recommendation against routinely using prophylactic or empiric antifungal therapy. This means the benefits of withholding these treatments likely outweigh the risks, but there’s still some uncertainty.
- Low-quality evidence from multiple randomized controlled trials showed no significant mortality benefit in administering antifungals prophylactically or empirically compared with placebo.
- Although IC carries substantial morbidity and mortality, its overall incidence in this population remains low, and ongoing surveillance or targeted diagnostics may be preferable to universal antifungal administration.
Conclusion: The panel emphasizes that these recommendations should be applied with clinical judgment, especially in patients with severe disease, likely high fungal burden, or concerns for antifungal resistance. Combination therapy for IPA may be particularly relevant when critical illness or limited triazole efficacy is suspected. Meanwhile, prophylactic or empiric anti-Candida therapy in the broader ICU setting does not appear to substantially reduce mortality. Continued advances in rapid diagnostics, close monitoring of local resistance patterns, and new antifungal agents may further refine best practices. Future research should focus on validating these findings in diverse patient populations, exploring novel combination regimens, and establishing more precise risk assessments for IC in the ICU.
Reference: Epelbaum O, Marinelli T, Haydour Q, Pennington KM, Evans SE, Carmona EM, Husain S, Knox KS, Jarrett BJ, Azoulay E, Hope WW, and others. “Treatment of Invasive Pulmonary Aspergillosis and Preventive and Empirical Therapy for Invasive Candidiasis in Adult Pulmonary and Critical Care Patients: An Official American Thoracic Society Clinical Practice Guideline.” American Journal of Respiratory and Critical Care Medicine (2025). https://doi.org/10.1164/rccm.202410-2045ST
Phase 2 RCT: Axatilimab Demonstrates Efficacy in Refractory Chronic GVHD by Targeting CSF1R-Dependent Macrophages
19 Sep, 2024 | 16:05h | UTCBackground: Chronic graft-versus-host disease (GVHD) is a significant long-term complication of allogeneic hematopoietic stem-cell transplantation, affecting approximately half of recipients and leading to substantial morbidity and mortality. Standard therapies often fail to induce durable responses in patients with refractory or recurrent disease. CSF1R-dependent monocytes and macrophages are key mediators of chronic GVHD, contributing to inflammation and fibrosis. Axatilimab, a CSF1R-blocking antibody, has shown promising activity in early studies.
Objective: To evaluate the efficacy and safety of axatilimab at three different doses in patients with recurrent or refractory chronic GVHD.
Methods: In this phase 2, multinational, randomized study (AGAVE-201), 241 patients aged ≥2 years with active chronic GVHD after at least two prior systemic therapies were randomized 1:1:1 to receive intravenous axatilimab at 0.3 mg/kg every 2 weeks (n=80), 1 mg/kg every 2 weeks (n=81), or 3 mg/kg every 4 weeks (n=80). Randomization was stratified by chronic GVHD severity and prior use of FDA-approved therapies (ibrutinib, ruxolitinib, or belumosudil). The primary endpoint was overall response rate (complete or partial response) within the first six cycles. The key secondary endpoint was a patient-reported reduction in symptom burden, defined as a decrease of more than 5 points on the modified Lee Symptom Scale (range 0–100).
Results: The overall response rate was 74% (95% CI, 63%–83%) in the 0.3 mg/kg group, 67% (95% CI, 55%–77%) in the 1 mg/kg group, and 50% (95% CI, 39%–61%) in the 3 mg/kg group, exceeding the predefined efficacy threshold in all groups. A clinically meaningful reduction in symptom burden was reported in 60%, 69%, and 41% of patients in the respective dose groups. Median time to response was less than 2 months across all groups. Organ-specific responses were observed in all affected organs, including skin, lungs, joints, and fascia.
The most common adverse events were dose-dependent transient laboratory abnormalities related to CSF1R blockade, such as elevations in liver enzymes and creatine kinase, which were not associated with clinical symptoms or end-organ damage. Periorbital edema occurred more frequently at higher doses. Adverse events leading to discontinuation occurred in 6% of patients in the 0.3 mg/kg group, 22% in the 1 mg/kg group, and 18% in the 3 mg/kg group. Serious infections were reported but were not dose-dependent.
Conclusions: Axatilimab demonstrated significant efficacy in patients with heavily pretreated recurrent or refractory chronic GVHD, with the highest response rates and best tolerability observed at the lowest dose tested (0.3 mg/kg every 2 weeks). Targeting CSF1R-dependent monocytes and macrophages may represent a novel therapeutic strategy in chronic GVHD.
Implications for Practice: Axatilimab offers a potential new treatment option for patients with chronic GVHD refractory to standard therapies, including those who have failed prior FDA-approved treatments. Clinicians should consider axatilimab as a therapeutic option while monitoring for transient laboratory abnormalities associated with CSF1R blockade. The lower dose appears to provide optimal efficacy with fewer adverse events.
Study Strengths and Limitations: Strengths include the randomized, multinational design and inclusion of patients with severe, refractory chronic GVHD who had received multiple prior therapies. Limitations include the lack of a comparator group, which may introduce outcome-reporting bias, and the small sizes of subgroups, limiting the generalizability of certain findings.
Future Research: Further studies are needed to confirm these results, assess long-term outcomes, and explore axatilimab in earlier lines of therapy and in combination with other treatments. Investigations into the use of axatilimab in other autoimmune diseases characterized by CSF1R-driven macrophage-mediated inflammation and fibrosis are also warranted.
RCT | Cyclophosphamide-based regimen enhances GVHD-free survival after hematopoietic stem-cell transplantation
27 Jun, 2023 | 13:54h | UTCSummary: The article details a phase 3 trial comparing the efficacy of two graft-versus-host disease (GVHD) prophylactic regimens in hematologic cancer patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT). The experimental group received cyclophosphamide–tacrolimus–mycophenolate mofetil, and the standard group received tacrolimus–methotrexate. The patients, a total of 431, underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched unrelated donor.
The primary end point was GVHD-free, relapse-free survival at 1 year. Results indicated a significantly higher incidence of this outcome in the experimental group (hazard ratio, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P=0.001). At 1 year, adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) in the experimental group, compared to 34.9% (95% CI, 28.6 to 41.3) in the standard group.
Notably, patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall survival, disease-free survival, relapse, transplantation-related death, and engraftment did not show a substantial difference between the groups. These results suggest that cyclophosphamide–tacrolimus–mycophenolate mofetil may offer a more effective prophylaxis against GVHD in HSCT patients.
Article: Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis – New England Journal of Medicine (link to abstract – $ for full-text)
News Release: Study Sets New Standard for Graft-Versus-Host Disease Prevention After Stem Cell Transplant – Johns Hopkins Medicine
Commentary on Twitter
In this trial, 1-year GVHD-free, relapse-free survival after stem-cell transplantation was 52.7% in the cyclophosphamide–tacrolimus–mycophenolate mofetil group and 34.9% in the tacrolimus–methotrexate group. https://t.co/wCdvP1LChu
— NEJM (@NEJM) June 21, 2023
Consensus Paper | Primary prophylaxis of invasive fungal diseases in patients with hematological malignancies
23 Jun, 2023 | 13:23h | UTC
Review | Acute graft-versus-host disease
14 Jun, 2023 | 14:20h | UTCAcute graft-versus-host disease – Nature Reviews Disease Primers (if the link is paywalled, try this one)
Commentary on Twitter
Tissue damage resulting from allogenic hematopoietic cell transplantation conditioning regimens triggers cellular interactions and #inflammatory cascades that lead to acute #GraftVersusHost disease symptoms https://t.co/iHyUVoV75J pic.twitter.com/ob9X7zQWB8
— Nature Reviews Disease Primers (@DiseasePrimers) June 11, 2023
DNA sequencing may identify an increased risk of relapse in adults with AML prior to hematopoietic cell transplantation
13 Mar, 2023 | 14:47h | UTCDNA Sequencing to Detect Residual Disease in Adults With Acute Myeloid Leukemia Prior to Hematopoietic Cell Transplant – JAMA (free for a limited period)
Commentary on Twitter
Among patients w AML in first remission prior to allogeneic hematopoietic cell transplant, the persistence of residual variants in the blood at an allele fraction ≥0.01% was assoc'd w increased relapse & worse survival vs those w/o these variants. https://t.co/KCnaQ1NRXJ
— JAMA (@JAMA_current) March 11, 2023
Review | Management of adult patients with hematological malignancies in critical care
10 Feb, 2023 | 13:45h | UTCManagement of adult patients with haematological malignancies in critical care – Anaesthesia
Cohort Study | Risk of malignant neoplasms of the gastrointestinal tract after blood or marrow transplant
30 Jan, 2023 | 00:23h | UTCMalignant Neoplasms of the Gastrointestinal Tract After Blood or Marrow Transplant – JAMA Oncology (link to abstract – $ for full-text)
Commentary: Risk of Subsequent Gastrointestinal Tract Malignancies After Blood or Marrow Transplantation – The ASCO Post
Commentary on Twitter
Exposure to cytarabine, etoposide and anthracyclines & chronic graft vs. host disease increase risk of colorectal, liver & esophageal cancer after BMT, providing evidence for appropriate evaluation & management in high-risk populations. https://t.co/UENFM1UWRw
— JAMA Oncology (@JAMAOnc) January 23, 2023
ASCO Guideline | Management of fever and neutropenia in pediatric patients with cancer and hematopoietic cell transplantation recipients
24 Jan, 2023 | 14:28h | UTC
An investigational T-cell therapy shows promise against six viral infections common after stem cell transplants
13 Jan, 2023 | 13:10h | UTC
Joint consensus statement on the vaccination of adult and pediatric hematopoietic stem cell transplant recipients.
30 Nov, 2022 | 13:39h | UTC
Consensus Paper | Hematopoietic cell transplantation in the management of myelodysplastic syndrome.
29 Nov, 2022 | 14:11h | UTC
Systematic Review | Stem cell transplantation for systemic sclerosis.
1 Aug, 2022 | 12:10h | UTCStem cell transplantation for systemic sclerosis – Cochrane Library
Summary: Stem cell transplantation for the treatment of systemic sclerosis – Cochrane Library
Cohort Study | Treatment outcomes and roles of transplantation and maintenance rituximab in patients with previously untreated mantle cell lymphoma.
5 Jul, 2022 | 11:39h | UTCNews Release: Mantle cell lymphoma treatment varies according to setting – Weill Cornell Medicine
Cohort Study: Burden of long-term morbidity borne by survivors of acute myeloid leukemia treated with blood or marrow transplantation.
29 Jun, 2022 | 10:56h | UTC
Commentary on Twitter
We must understand life after BMT better, what it MEANS for a patient surviving intensive but curative treatment. Kudos to this @JCO_ASCO paper but we need better designs: versus other treatments, in BMT cohorts!
Life's gray, not categorical…#bmtsmhttps://t.co/E4YQV4LzoN pic.twitter.com/P7bMWXMTB5— Nico Gagelmann (@NicoGagelmann) June 23, 2022
Under a https://creativecommons.org/licenses/by-nc-nd/4.0/ license
Bring it on: Top five antimicrobial stewardship challenges in transplant infectious diseases and practical strategies to address them.
29 Apr, 2022 | 10:51h | UTC
Commentary on Twitter
🆕💥Review Article @ASHE_Journal
Bring it on: Top five antimicrobial stewardship challenges in transplant infectious diseases and practical strategies to address them #IDTwitter #medtwitter #TwitteRx #MedEd https://t.co/ToPLQXtC4r pic.twitter.com/pZQWWb3ZSx— Antibiotic Steward Bassam Ghanem 🅱️C🆔🅿️🌟 (@ABsteward) April 28, 2022
Under a http://creativecommons.org/licenses/by/4.0/ license
Pre-transplant EASIX (endothelial activation and stress index) may predict the hazard of sepsis after allogeneic stem cell transplantation.
19 Apr, 2022 | 02:04h | UTCPre-transplant EASIX and sepsis after allogeneic stem cell transplantation – Intensive Care Medicine
Commentary on Twitter
🧪 Endothelial complications major causes of mortality post alloSCT. Pre Tx Endothelial Activation & Stress IndeX EASIX (basic lab data characterizing Tx-associated thrombotic microangiopathy) powerful marker of #sepsis, dysfunctional endothelial response.https://t.co/FRGUGT8L78 pic.twitter.com/VF2wTLCHaM
— Intensive Care Medicine (@yourICM) April 18, 2022
A single-arm study evaluated Naive T-Cell depleted peripheral blood stem-cell grafts for the prevention of chronic graft-versus-host disease.
19 Jan, 2022 | 08:22h | UTCNaive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease – Journal of Clinical Oncology
Commentary: New graft strategy may improve outcomes for blood stem cell recipients – University of Pittsburg
RCT: Maribavir for refractory Cytomegalovirus infections with or without resistance post-transplant.
7 Dec, 2021 | 08:37h | UTC
ASH 2021 guidelines for stem cell transplantation in patients with sickle cell disease.
14 Oct, 2021 | 09:53h | UTCNews release: ASH Releases New Clinical Practice Guidelines on Stem Cell Transplantation in Sickle Cell Disease
Commentary: ASH Issues Guideline on the Use of HSCT for Sickle Cell Disease – HealthDay
FDA authorizes additional Covid-19 vaccine dose for certain immunocompromised individuals – Other fully vaccinated individuals do not need an additional vaccine dose right now.
16 Aug, 2021 | 01:22h | UTCCommentaries:
CDC, FDA recommend COVID booster for immune-compromised – CIDRAP
FDA authorizes additional dose of Covid-19 vaccine for the immunocompromised – STAT
Covid booster: US approves third jab for the immunocompromised – BBC
CDC Panel Recommends 3rd Vaccine Dose For Immunocompromised People – NPR
6 Things To Know If You’re Immunocompromised And Considering A 3rd Shot – NPR
CDC recommends third Covid-19 vaccine dose for certain immunocompromised people – CNN
Commentary on Twitter
The Infectious Diseases Society of America (IDSA) supports the @FDA and @CDCgov's decision to authorize a supplemental vaccine dose for immunocompromised patients.
Read our statement: https://t.co/odzzSgIxnY pic.twitter.com/4PZfUwpjhM
— IDSA (@IDSAInfo) August 13, 2021
RCT: Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease.
16 Jul, 2021 | 10:37h | UTC
Review: Care for the organ transplant recipient on the intensive care unit
8 Apr, 2021 | 08:36h | UTCCare for the organ transplant recipient on the intensive care unit – Journal of Critical Care
Review: Post-Transplant Pregnancy and Contraception
23 Mar, 2021 | 02:10h | UTCPost-Transplant Pregnancy and Contraception – Clinical Journal of the American Society of Nephrology
Short review: Acute CV complications of hematopoietic stem cell transplantation
18 Feb, 2021 | 02:40h | UTCAcute CV Complications of Hematopoietic Stem Cell Transplantation – American College of Cardiology