Introduction:

• It is tissue damage by donor T cells with specificity for recipient antigens that are not expressed in donor.

Types

• Acute- GVHD occurring before 100 days
• Chronic- GVHD occurring after 100 days
• But overlaps may be seen

Incidence:

• Sibling transplant- 26-32%
• MUD- 42-52%

Risk factors:

• Disparity in HLA typing
• Older age
• Gender disparity (Higher risk, especially if donor is female)
• Higher number of T cells in graft
• Type of immune prophylaxis used
• Gut decontamination- Provides some protection against GVHD
• Source of stem cells- Contraversial data (Some feel PBSC is associated with high risk of GVHD)

Pathogenesis:

Host antigen presenting cells are activated by proinflammatory cytokines such as TNF alpha and IL 1, which are released following tissue damage induced by conditioning regimen

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Antigen presenting cells upregulate the surface expression of co-stimulatory molecules and HLA molecules loaded with peptides derived from host antigens

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Activation of donor T cells (Both CD4 and CD8 cells)

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Development and proliferation of donor T cells

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Secretion of activating cytokines such as TNF alpha and interferon gamma

Induction of perforin/ Fasligand pathways which cause cellular cytotoxicity

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Recruitment of neutrophils, eosinophils, macrophages and NK cells

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Epithelial injury

Acute GVHD

Clinical features:

• Rash- maculopapular type, commonly involves palms and soles and scalp is spared. Severe cases there is erythroderma, bullae formation and painful blistering
• Gut GVHD- Diarrhoea, nausea, vomiting, abdominal pain, bleeding due to mucosal ulceration
• Liver GVHD- Deranged LFT (Cholestatic pattern), painful hepatomegaly, dark urine and pale stools

Glucksberg Grading:

Overall grade:

Investigations:

• Early biopsy- It will help in ruling out other differential diagnosis and helps in institution of appropriate therapy. Changes seen include:
  • Individual cell necrosis
  • Loss of crypts with apoptotic bodies at crypt bases
  • Ulceration
  • Perivascular infiltration of lymphocytes

Prevention: Refer to previous section

Treatment:

Grade 1-

• Topical steroids- Betnovate cream- BD
• For resistant cases- Topical tacrolimus- 0.1% cream, then wean with 0.03% cream.
• Optimize cyclosporine A levels

For further grades:

• Optimize Cyclosporine A levels
• 1^st line therapy:
  • Steroids are standard first line therapy
  • Methyl prednisolone/ Prednisolone- 2mg/Kg/Day for 7-14 days, then subsequent tapering (atleast over 8 weeks).
  • Response rate- 44%.
  • Transplant related mortality is very high in patients who do not respond to steroids.
  • 2 types of failures to corticosteroid therapy
    • True steroid resistance- Progression of GVHD manifestations while patient isreceiving full dose corticosteroids or no response after 5 days of starting steroids. Overall 1 year survival is <10% in these patients.
    • Steroid dependence- Reoccurrence of GVHD during or after tapering of steroid treatment
  • Gut involvement: Oral beclomethasone/ Budesonide with Octreotide
• 2^nd line agents: Added if there is no improvement after 5 days or progression within 72 hrs of starting steroids. If patient fails one second line agent, another second line therapy must be used prior to moving to third line options. 2^nd line agents are usually given along with steroids.
  • Extracorporeal photopheresis
    • 15% of patient’s blood is withdrawn in each cycle and buffy coat is isolated. To this 8 methoxypsoralen is added and exposedto UV radiation and returned to patient.
    • ECP induces apoptosis of all leucocytes, including activated T cells within 24hrs of return. Immune homeostasis is maintained through modulation of cytokine production and tolerance induction of antigen presenting cells.
    • Weekly cycles for minimum of 8 weeks is given.
    • It is not very useful in acute GVHD.
    • Machine used- UVAR XTS (Therakos, Ascot, UK)
    • Excellent safety profile
    • Side effects- Hypotension, fever, reduced hemoglobin
  • IL2- Antibodies (Useful in skin GVHD)
    • Baciliximab: Dose- 20mg-IV- on days 1 and 4.
    • Daclizumab, Inolimomab
    • Response rate- 71%
  • Anti-TNF antibodies (Useful in GI GVHD)
    • Infliximab
      • Dose: 10mg/Kg/Day IV- Weekly for 1-4 weeks
    • Etanercept
      • Dose: 0.4mg/Kg- SC- Twice weekly for 4-8 weeks (Max dose- 25mg)
    • Associated with increased risk of infection
    • Response rate- 75%
  • Sirolimus
    • Useful in Skin, GI and liver GVHD
    • Dose: Loading dose of 3-8mg, followed by maintainance of 1-2mg/day. Adjust the dose to maintain trough level of 4-12ng/mL
    • Response rate- 57%
    • Side effects- Myelosuppression, seizures, HUS
    • Use with caution along with cyclosporine
    • Dose reduction is needed when used along with azoles (40-50%)
    • Monitoring of drug levels is needed at least once a week. Target level- 4-8ng/ml
  • Mycophenolate mofetil
    • 1.5 to 3gm/day in 2 divided doses
    • Useful in skin and liver GVHD
  • Tacrolimus
  • Tocilizumab:
    • Dose: 8mg/Kg- IV every 2 weeks untill CR (Maximum of 6 doses)
  • Methotrexate
    • Dose- 5mg/m2- Once a week
    • Response rate- 81%
  • Ruxolitinib
    • Starting dose- 5-10mg- BD
    • Useful in skin, GI and liver GVHD
  • Mesenchymal stem cells
    • Undifferentiated pleuripotent stem cells that modulate immune and inflammatory response and facilitate repair of connective tissues
    • 1-10X10^6/Kg recipient body weight 
    • Useful in GI and Liver GVHD
    • Response rate- 40%
  • Alpha 1 antitrypsin:
    • Dose: 60mg/Kg IV daily for up to 4 consecutive weeks on days 1, 4, 8, 12, 16, 20, 24 and 28 (Maximum- 8 does)
    • Useful in skin, GI and liver GVHD
  • Fecal microbiota transplant
    • Useful in GI GVHD
• 3^rd line agents:
  • Alemtuzumab
    • Dose- 10mg- SC-OD for 5 days
    • Useful in skin and liver GVHD
  • Pentostatin
    • 1.5mg/m2/day for 3 days
    • Response rate- 50%
• Agents that are not recommended
  • ATG
  • Rituximab
  • Visiluzumab
  • Thalidomide
  • Azathioprine

Chronic GVHD

• It is the leading cause of non-relapse death.
• For treatment of chronic GVHD patients, a multidisciplinary team of specialists with special interest in GVHD must be established comprising of dermatologist, oral physician, gastroenterologist, ophthalmologist, respiratory physician, endocrinologist, infectious disease specialist, physiotherapist, psychologist and dietician.
• Risk factors for increased mortality
  • Extensive skin GVHD involving >50% of body surface area
  • Platelet count <1lac/cmm
  • Progressive acute GVHD that continues uninterrupted beyond 100 days.
• For mild disease only local treatment is sufficient. For moderate and severe disease systemic therapy is indicated. 
• Systemic agents for treating chronic GVHD are same as those used in acute GVHD. Following are additional agents which are used in chronic GVHD
  • Imatinib- Has best results in sclerotic skin lesions. Useful in patients with mild to moderate bronchiolitisobliterans. Dose- 100-200mg- OD. Increase to 400mg- OD if well tolerated.
  • Thalidomide
  • Azathioprine
  • Retinoids- Useful in case of skin lesions
  • Rituximab- Useful in case of autoantibody mediated manifestations. Dose- 50-375mg/m2- once a week for 4 doses.
  • Prednisolone in chronic GVHD- 1mg/Kg for 2-3 months, then reduce dose by 10-20% every month (total duration of 9 months). If other immunosuppression is added, then steroids must be tapered first. Cyclosporine with steroids is the best combination. Avoid third drug if patient is on steroid- Cyclosporine A combination.
• Immunosuppression must be continued for 2-3 years in patients who develop chronic GVHD.
• Other agents that are not recommended for routine use.
  • Hydroxychloroquine- Used in skin, liver and oral GVHD.
  • Clofazimine- Used in skin GVHD
  • Cyclophosphamide
  • Thoraco abdominal irradiation
• Antimicrobial prophylaxis must be given when patient is receiving treatment, which includes- Penicillin V, Voriconazole/Posaconazole, Cotrimoxazole, Acyclovir.
• They should also receive following vaccines
  • Pneumococcus- 3-6 months post transplant
  • Influenza- At 4-6 months, and then repeated on annual basis.
  • Hemophilusinfluenzae- 6-12 months post transplant

Individual organ GVHD and additional measures:

NIH Grading of chronic GVHD: Scoring for each system 

1. No involvement
2. Mild impairment
3. Moderate impairment
4. Severe impairment

Grading

• Mild- Involvement of 1-2 organs with score of 1 and no pulmonary involvement
• Moderate- Involvement of 3 organs with score 1, or at least 1 organ with score 2.
• Severe- Score 3 in any organ or pulmonary score of 2

Recent advances:

Belumosudil in Chronic GVHD 

Belumosudil is a new selective inhibitor of ROCK2 kinase. It suppresses type 17 and follicular T helper cells through downregulation of STAT-3. At the same time it enhances the regulatory T cells through upregulation of STAT5. Belumosudil was studies in patients with chronic GVHD who had received 2-5 prior lines of therapy. With a dose of 200mg- OD, the overall response rate was 74%. Adverse events were similar to those with other immunosuppressants. Only 12% patients discontinued treatment due to drug related adverse effects. 44% patients continued treatment beyond 1 year. 

https://doi.org/10.1182/blood.2021012021  

Off the shelf Mesenchymal stem cells in treatment of acute GVHD  

A study from Japan evaluated Temcel (cryopreserved, human BM derived Mesenchymal stem cells) in management of acute GVHD. Total of 381 patients received a median dose of 2x10⁶ cells/kg. Median number of infusions were 8. ORR on day 28 after start of therapy was 56%. When it was used as second line therapy after steroids, ORR was 61%. Overall survival at 6 months was 40%.  

https://doi.org/10.1038/s41409-021-01304-y 

Fludarabine/busulfan versus busulfan/cyclophosphamide as myeloablative conditioning for myelodysplastic syndrome

The effectiveness of Flu/Bu for myelodysplastic syndrome remains poorly understood. A study from Japan, analysed registry data from 2006 to 2018 and compared transplant outcomes of adult MDS patients receiving Flu/Bu and busulfan/cyclophosphamide using propensity score matching. The 3-year OS rates were 52.7% and 49.5% in the Flu/Bu and Bu/Cy group. They concluded Flu/Bu could be an alternative to Bu/Cy for MDS patients prior to allo-HSCT. 

https://doi.org/10.1038/s41409-021-01447-y

Omission of day +11 methotrexate dose and allogeneic hematopoietic cell transplantation outcomes

When mucositis and organ toxicity develop, the day +11 dose is frequently omitted to limit further organ damage. A metanalysis was conducted to study effect of this practice on overall outcome. Pooled OS rate favored those who received day +11 methotrexate vs. those who did not. There was no significant difference in pooled rates of PFS, acute GVHD, chronic GVHD, and relapse between the two groups. 

https://doi.org/10.1038/s41409-021-01496-3

Leukemia inhibitory factor protects against GVHD while preserving GVL activity 

Administrating recombinant LIF protein protects mice from GVHD-induced tissue damage and lethality without compromising the graft-versus-leukemia activity, which is crucial to prevent tumor relapse. The study found that rLIF decreases the infiltration and activation of donor immune cells and protects intestinal stem cells to ameliorate GVHD. 

https://doi.org/10.1182/blood.2022015677  

Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease

Present study evaluated 266 allo-HCT recipients from whom 1303 stool samples were profiled by 16S ribosomal gene sequencing. Patients were classified according to which organs were affected by aGVHD. GI GVHD patients showed significant reduction in microbial diversity preonset. Findings of this study suggest that the intestinal microbiome can serve as a biomarker for outcomes of allo-HCT patients with GVHD.

https://doi.org/10.1182/blood.2021015352

Itacitinib monotherapy for low-risk acute GVHD 

The standard primary treatment for acute graft-versus-host disease (GVHD) requires prolonged, high-dose systemic corticosteroids (SCSs) that delay reconstitution of the immune system. We used validated clinical and biomarker staging criteria to identify a group of patients with low-risk (LR) GVHD that is very likely to respond to SCS. Present study tested use of itacitinib, a selective JAK1 inhibitor, in treatment of LR GVHD. (itacitinib 200 mg/d for 28 days). Contrrol group received systemic steroids. Response rates at day 28 were very high for both groups (89% vs 86%, P = .67). Fewer itacitinib-treated patients developed a serious infection within 90 days (27% vs 42%, P = .04). 

https://doi.org/10.1182/blood.2022017442 

Interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract 

Present study evaluated the safety and efficacy of a novel recombinant human interleukin-22 dimer, F-652, used in combination with systemic corticosteroids for treatment of newly diagnosed lower gastrointestinal acute GVHD. The most common adverse events were cytopenias and electrolyte abnormalities, and there were no dose-limiting toxicities. Out of 27 patients, 19 achieved a day-28 treatment response, meeting the prespecified primary endpoint. 

https://doi.org/10.1182/blood.2021015111

Reduced-dose post-transplant cyclophosphamide plus low-dose post-transplant anti-thymocyte globulin as graft-versus-host disease prophylaxis with fludarabine–busulfan–cytarabine conditioning in haploidentical peripheral blood stem cell transplantation

This multicentre, randomized clinical trial was conducted to determine the efficacy of reduced-dose PTCy (40 mg/kg/d on days 3 and 4) combined with low-dose post-transplant ATG (2.5 mg/kg on day 8)-based GVHD prophylaxis (reduced-dose PTCy/ATG) with fludarabine–busulfan–cytarabine (FBA) conditioning for patients with haematological malignancies. From 2018 to 2022, 122 patients from four institutions were randomly assigned 1:1 to either a reduced-dose PTCy/ATG or a standard-dose ATG group (‘Beijing Protocol’, ATG: 10 mg/kg). All patients achieved myeloid engraftment. Cumulative incidences of grade II–IV (11.5% vs 39.3%) and grade III–IV (6.6% vs 24.6%) acute GVHD at day 100 were significantly reduced in the reduced-dose PTCy/ATG group. Furthermore, two-year overall survival, disease-free survival and GVHD-free/relapse-free survival were significantly improved in the reduced-dose PTCy/ATG group (75.4% vs 54.1% respectively). 

https://doi.org/10.1111/bjh.18483 

Effective treatment of low-risk acute GVHD with itacitinib monotherapy

Itacitinib, is a selective JAK1 inhibitor. In the present study, 70 patients with LR GVHD were treated with 28 days of itacitinib 200 mg/d, and  compared with outcomes of 140 contemporaneous, matched control patients treated with systemic steroids. Study showed that, itacitinib monotherapy is a safe and effective alternative to systemic steroid treatment for LR GVHD.

https://doi.org/10.1182/blood.2022017442

Vedolizumab for children with intestinal graft-versus-host disease

This report highlights the use of vedolizumab, an anti-α4β7 integrin antibody, as a potential treatment for steroid-refractory intestinal acute graft-versus-host disease (aGVHD) in pediatric patients. The case study involves a male patient with late-onset aGVHD following an allogeneic cord blood transplantation for WHIM syndrome. After being refractory to steroids, vedolizumab was administered, leading to the alleviation of aGVHD symptoms and improved endoscopic findings. The report also evaluates vedolizumab's efficacy in a total of 10 patients with intestinal aGVHD, showing a 60% objective response rate and no serious adverse events.

https://doi.org/10.1007/s12185-023-03590-2

Higher abatacept exposure after transplant decreases acute GVHD risk without increasing adverse events

The ABA2 study evaluated abatacept, a T-cell costimulation blockade agent, for preventing acute graft-versus-host disease (aGVHD) after unrelated-donor hematopoietic cell transplant. The dosing regimen aimed for a steady-state trough of 10 μg/mL, but a higher trough (≥39 μg/mL) was linked to reduced risk of grade 2-4 aGVHD. A trough below 39 μg/mL yielded a similar aGVHD risk to placebo. Importantly, higher abatacept troughs did not correlate with adverse events or other safety concerns. This data suggests a favorable correlation between higher abatacept trough levels and reduced aGVHD risk, without increased toxicity.

https://doi.org/10.1182/blood.2023020035

Red cell distribution width as a new prognostic biomarker in refractory chronic graft-versus-host disease

The study introduces red cell distribution width (RDW) as a potential biomarker for predicting outcomes in patients with chronic graft-versus-host disease (cGvHD) following allogeneic hematopoietic cell transplantation. RDW values ≥13.4% were associated with lower overall survival and higher non-relapse mortality. RDW may serve as an accessible biomarker for risk stratification in cGvHD patients, offering valuable prognostic information. 

https://doi.org/10.3324/haematol.2023.283646

Impact of metabolic syndrome on outcomes in patients with chronic graft-versus-host disease

The study evaluated adult patients (n = 229) with chronic graft-versus-host disease (cGVHD) for the prevalence and impact of metabolic syndrome (MetS). A majority (54.1%) of the cohort met the diagnostic criteria for MetS. Patients with higher body mass index and lower performance status scores were more likely to have MetS. Higher circulating erythrocyte sedimentation rate, C-reactive protein, and creatinine concentrations, along with lower estimated glomerular filtration rate, were associated with MetS. However, patients with MetS compared to those without MetS had no statistical differences in survival or non-relapse mortality. 

https://doi.org/10.1038/s41409-023-02097-y

Low- versus standard-dose post-transplant cyclophosphamide as GVHD prophylaxis for haploidentical transplantation

In a retrospective analysis comparing standard-dose (100 mg/kg) post-transplant cyclophosphamide (PTCY) with reduced-dose (80 mg/kg) PTCY in haploidentical hematopoietic cell transplantation (haplo-HCT), 969 patients received standard dose while 538 received reduced dose. After propensity score matching, 425 patients were included in each group. There was no significant difference in 2-year overall survival (OS) between standard-dose (55.9%) and reduced-dose (47.0%) groups (p = 0.36), nor in the cumulative incidence of 2-year non-relapse mortality (standard-dose 21.3%, reduced-dose 20.5%; p = 0.55). Rates of acute and chronic graft-versus-host disease (GVHD) were similar between the two groups. 

https://doi.org/10.1111/bjh.19228

Fecalmicrobiota transplantation in capsules for the treatment of steroid refractory and steroid dependent acute graft vs. host disease

In a prospective pilot study, 21 patients with steroid-resistant or steroid-dependent lower gastrointestinal acute graft-versus-host disease (aGvHD) received fecalmicrobiota transplantation (FMT) in capsule form. The overall response rate at 28 days after the first FMT was 52.4%, with complete and partial responses observed in 23.8% and 28.6% of patients, respectively. However, sustained responses were rare, with only one patient remaining aGvHD-free long-term

https://doi.org/10.1038/s41409-024-02198-2

Oral vitamin A for graft-versus-host disease in children and young adults

In a randomized clinical trial involving 80 recipients of hematopoietic stem cell transplantation (HSCT), pretransplant high-dose vitamin A administration resulted in a lower incidence of acute and chronic graft-versus-host disease (GVHD) compared to placebo. While the primary endpoint of acute GVHD incidence at day +100 did not reach statistical significance, there was a trend towards lower incidence, particularly in acute gastrointestinal (GI) GVHD. In an "as treated" analysis, recipients of vitamin A had significantly lower cumulative incidence of acute GI GVHD and chronic GVHD compared to placebo

https://doi.org/10.1182/blood.2023022865

ATG or post-transplant cyclophosphamide to prevent GVHD in matched unrelated stem cell transplantation?

In adult recipients of peripheral blood allogeneic stem cell transplants (alloSCTs) from 10/10 antigen-matched unrelated donors (MUD), post-transplantation Cyclophosphamide (PTCy) prophylaxis demonstrated favorable outcomes compared to rabbit anti-thymocyte globulin (rATG) prophylaxis. PTCy showed lower non-relapse mortality (NRM) at 2 years (12.1% vs. 16.4%; p=0.016; HR 0.72), reduced relapse rates (22.8% vs. 26.6%; p=0.046; HR 0.87), and improved overall survival (73.1% vs. 65.9%; p=0.001, HR 0.82) and progression-free survival (64.9% vs. 57.2%; p<0.001, HR 0.83). Additionally, PTCy was associated with lower incidence of chronic GVHD and higher GVHD-free relapse-free survival compared to rATG.

https://doi.org/10.1038/s41375-024-02225-7

Post-Transplant Cyclophosphamide–Based GVHD Prophylaxis attenuates disparity in outcomes between use of matched or mismatched unrelated donors

This study assessed the impact of post-transplant cyclophosphamide (PTCy) versus calcineurin inhibitor (CNI) prophylaxis in hematopoietic cell transplantation (HCT) using HLA-matched (MUD) or mismatched unrelated donors (MMUD). Among 10,025 patients, PTCy improved overall survival (OS) and GVHD-free, relapse-free survival (GRFS) compared to CNI-based regimens, with no significant difference between MUD and MMUD transplants. The findings highlight that PTCy expands donor options and provides comparable outcomes, enhancing HCT accessibility across different racial and ethnic groups.

https://doi.org/10.1200/JCO.24.0018

Novel MAGIC composite scores using both clinical symptoms and biomarkers best predict treatment outcomes of acute GVHD

A new grading system for acute graft-versus-host disease (GVHD) was developed to include a low-risk category based on clinical symptoms, addressing the limitations of existing systems like the Minnesota risk classification. Using data from the Mount Sinai Acute GVHD International Consortium (MAGIC), three Manhattan risk groups were created through a classification and regression tree (CART) algorithm, improving prediction of 6-month nonrelapse mortality (NRM). When serum GVHD biomarkers were incorporated, the MAGIC composite scores further enhanced prognostic accuracy. The MAGIC composite score effectively predicted treatment response and long-term outcomes, offering a more precise tool for guiding GVHD management and trial design.

https://doi.org/10.1182/blood.2024025106

Treatment of newly diagnosed moderate or severe chronic graft-versus-host disease with prednisone and everolimus

In this phase II trial, patients with newly diagnosed moderate or severe chronic GVHD (cGVHD) were treated with prednisone and everolimus. At 6 months, 56% achieved treatment success (alive, with partial or complete response, no relapse, and no need for secondary therapy). A high response rate (88%) was observed, with most responses occurring within 6 weeks. By 1 year, treatment success decreased to 37% due to relapses. No severe side effects like thrombotic microangiopathy or pneumonitis were reported, indicating that everolimus addition is well-tolerated and may enhance long-term cGVHD management, pending further study.

https://doi.org/10.1038/s41409-024-02289-0

Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease

In this phase 2 study, the CSF1R-blocking antibody axatilimab was tested in patients with recurrent or refractory chronic graft-versus-host disease (GVHD). Overall response rates were 74% for the 0.3 mg group, 67% for the 1 mg group, and 50% for the 3 mg group. Significant symptom improvement was observed in 60% and 69% of patients in the 0.3 mg and 1 mg groups, respectively. Axatilimab demonstrated a favorable safety profile, particularly at the 0.3 mg dose, suggesting it is a promising option for treating chronic GVHD.

https://doi.org/10.1056/NEJMoa2401537

Posttransplantcyclophosphamide in unrelated and related peripheral blood stem cell transplantation from HLA-matched and 1 allele mismatched donor

The prospective multicenter phase II study evaluated posttransplantcyclophosphamide (PTCy) with tacrolimus and mycophenolatemofetil in 43 patients undergoing peripheral blood stem cell transplantation (PBSCT) with varying degrees of HLA matching and conditioning intensity. The incidence of grade III–IV acute GVHD at 100 days was low at 2.3%, with manageable rates of acute and chronic GVHD at 2 years. Overall survival and disease-free survival at 2 years were favorable, with a low non-relapse mortality rate. GVHD-free, relapse-free survival at 2 years was also promising, and a high percentage of patients were able to discontinue immunosuppressants at 2 years post-transplant. These findings suggest that PTCy is an effective option for GVHD prophylaxis in both HLA-matched and HLA-mismatched PBSCT.

https://doi.org/10.1038/s41409-023-02162-6

ECP versus ruxolitinib in steroid-refractory chronic GVHD

The study aimed to compare the effectiveness of ruxolitinib and extracorporeal photophoresis (ECP) in treating steroid-refractory and steroid-dependent chronic GVHD (SR-cGVHD). Data from 31 EBMT centers were collected on patients treated with either ECP or ruxolitinib between January 2017 and July 2019. Multivariate analyses adjusted for GVHD grading and type showed no significant difference in overall response rates between the two groups at day+180. Similarly, no significant differences were observed in overall survival, progression-free survival, non-relapse mortality, or relapse incidence.

https://doi.org/10.1038/s41409-023-02174-2

Ruxolitinib in steroid-refractory acute graft-vs-host disease

This study compared ruxolitinib to best available therapy (BAT) in Japanese patients with steroid-refractory acute graft-versus-host disease. The overall response rate (ORR) at day 28 was higher with ruxolitinib (88.9%) versus BAT (52.4%). Median failure-free survival was longer with ruxolitinib (2.73 vs. 1.25 months). Common adverse events included anemia (55.6% with ruxolitinib vs. 19.0% with BAT).

https://doi.org/10.1007/s12185-024-03772-6

Belumosudil as second or subsequent line of therapy for steroid-dependent/steroid-resistant chronic GVHD

This study assessed belumosudil mesylate (200 mg daily), a selective ROCK2 inhibitor, as a second or subsequent therapy for steroid-dependent/resistant chronic graft-versus-host disease in 21 Japanese patients aged ≥12 years. The overall response rate (ORR) at 24 weeks was 85.7%, exceeding the predefined efficacy threshold. Responses were sustained for ≥20 weeks in 72.2% of responders, with improvements observed in joints/fascia (80%), mouth (66.7%), and skin (54.5%). Corticosteroid dose reductions were achieved in 57.1% of patients. Most common treatment-emergent adverse event was diarrhea (19.0%), with no drug-related discontinuations or deaths. 

https://doi.org/10.1002/ajh.27424

Ruxolitinib for Treatment of Corticosteroid Refractory Sclerotic Chronic Graft-Versus-Host Disease

In this phase II trial, ruxolitinib was evaluated in 47 patients with refractory sclerotic cGVHD. Partial responses in skin and/or joints were observed in 49% at six months, with a 77% response duration at 12 months. Overall cGVHD response was 47%, with improved patient-reported outcomes and high failure-free survival (77% at 12 months). Ruxolitinib was well tolerated, showing promise as an effective treatment option.

https://doi.org/10.1200/JCO.24.00205