Difference between revisions of "Graft versus host disease"

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===References===
 
===References===
 
# Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, Volin L, Ruutu T, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhäuser M, Einsele H, Kolb HJ, Bertz H, Egger M, Grishina O, Socié G; ATG-Fresenius Trial Group. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009 Sep;10(9):855-64. Epub 2009 Aug 18. [https://www.ncbi.nlm.nih.gov/pubmed/19695955 PubMed]
 
# Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, Volin L, Ruutu T, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhäuser M, Einsele H, Kolb HJ, Bertz H, Egger M, Grishina O, Socié G; ATG-Fresenius Trial Group. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009 Sep;10(9):855-64. Epub 2009 Aug 18. [https://www.ncbi.nlm.nih.gov/pubmed/19695955 PubMed]
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==Methotrexate, Tacrolimus, Vorinostat {{#subobject:ca16a7|Regimen=1}}==
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{| class="wikitable" style="float:right; margin-left: 5px;"
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|-
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|[[#top|back to top]]
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|}
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===Regimen {{#subobject:191ac5|Variant=1}}===
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{| border="1" style="text-align:center;" !align="left"
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|'''Study'''
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|[[Levels_of_Evidence#Evidence|'''Evidence''']]
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|-
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|[http://www.bloodjournal.org/content/130/15/1760.long Choi et al. 2017]
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|style="background-color:#eeee00"|Phase II
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====Immunosuppressive therapy====
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*[[Methotrexate (MTX)]] 5 mg/m<sup>2</sup> IV once per day on days +1, +3, +6, +11
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*[[Tacrolimus (Prograf)]] by one of the following routes, starting on day -3:
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**IV: 0.03 mg/kg/day
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**PO: 0.045 mg/kg/day
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**Goal trough level of 8 to 12 ng/mL
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**In absence of GVHD, tapering begins on day +100 and completes on day +180
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*[[Vorinostat (Zolinza)]] 100 mg PO BID on days -10 to +100
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===References===
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# Choi SW, Braun T, Henig I, Gatza E, Magenau J, Parkin B, Pawarode A, Riwes M, Yanik G, Dinarello CA, Reddy P. Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT. Blood. 2017 Oct 12;130(15):1760-1767. Epub 2017 Aug 7. [http://www.bloodjournal.org/content/130/15/1760.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28784598 PubMed]
  
 
==Rabbit ATG==
 
==Rabbit ATG==

Revision as of 21:51, 17 October 2017

Prevention

This is very basic for now, potentially to expand in the future.

Cyclosporine, Methotrexate, ATG

References

  1. Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, Volin L, Ruutu T, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhäuser M, Einsele H, Kolb HJ, Bertz H, Egger M, Grishina O, Socié G; ATG-Fresenius Trial Group. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009 Sep;10(9):855-64. Epub 2009 Aug 18. PubMed

Methotrexate, Tacrolimus, Vorinostat

back to top

Regimen

Study Evidence
Choi et al. 2017 Phase II

Immunosuppressive therapy

  • Methotrexate (MTX) 5 mg/m2 IV once per day on days +1, +3, +6, +11
  • Tacrolimus (Prograf) by one of the following routes, starting on day -3:
    • IV: 0.03 mg/kg/day
    • PO: 0.045 mg/kg/day
    • Goal trough level of 8 to 12 ng/mL
    • In absence of GVHD, tapering begins on day +100 and completes on day +180
  • Vorinostat (Zolinza) 100 mg PO BID on days -10 to +100

References

  1. Choi SW, Braun T, Henig I, Gatza E, Magenau J, Parkin B, Pawarode A, Riwes M, Yanik G, Dinarello CA, Reddy P. Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT. Blood. 2017 Oct 12;130(15):1760-1767. Epub 2017 Aug 7. link to original article contains verified protocol PubMed

Rabbit ATG

References

  1. Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, Gallagher G, Kerr H, Kuruvilla J, Lee SJ, Moore J, Nevill T, Popradi G, Roy J, Schultz KR, Szwajcer D, Toze C, Foley R; Canadian Blood and Marrow Transplant Group. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol. 2016 Feb;17(2):164-173. Epub 2015 Dec 24. PubMed
  2. Locatelli F, Bernardo ME, Bertaina A, Rognoni C, Comoli P, Rovelli A, Pession A, Fagioli F, Favre C, Lanino E, Giorgiani G, Merli P, Pagliara D, Prete A, Zecca M. Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1126-1136. Epub 2017 Jul 10. PubMed

Scoring

Glucksberg acute graft versus host (GVHD) scores

Skin

  • Stage 0: No rash
  • Stage 1: Maculopapular rash <25% of body surface area
  • Stage 2: Maculopapular rash on 25-50% of body surface area
  • Stage 3: Generalized erythroderma
  • Stage 4: Generalized erythroderma with bullous formation and desquamation

Liver

  • Stage 0: Bilirubin <2 mg/dL
  • Stage 1: Bilirubin 2-3 mg/dL
  • Stage 2: Bilirubin 3.01-6 mg/dL
  • Stage 3: Bilirubin 6.01-15.0 mg/dL
  • Stage 4: Bilirubin >15 mg/dL

GI

  • Stage 0: No diarrhea, or diarrhea <500 mL/day
  • Stage 1: Diarrhea 500-999 mL/day
  • Stage 2: Diarrhea 1000-1499 mL/day
  • Stage 3: Diarrhea >1500 mL/day
  • Stage 4: Severe abdominal pain, with or without ileus

Glucksberg grade

Overall grade I II III IV
Skin 1-2 1-3 2-3 2-4
GI 0 1 2-3 2-4
Liver 0 1 2-4 2-4
Karnofsky performance scale 90-100% 70-80% 50-60% 30-40%

IBMTR severity index

The severity is the highest level which the patient reaches based on separate skin, liver, and GI staging.

Overall grade A B C D
Skin 1 2 3 4
GI 0 1-2 3 4
Liver 0 1-2 3 4

Chronic GVHD

Localized

  • Localized skin and/or liver dysfunction due to chronic GVHD

Extensive

  • Generalized skin involvement or localized skin and/or liver dysfunction due to chronic GVHD plus at least one of the following:
    • Liver biopsy showing cirrhosis, chronic aggressive hepatitis, bridging necrosis
    • Eye involvement, defined as Schirmer's test with <5 mm wetting
    • Involvement of oral mucosa on lip biopsy or minor salivary glands
    • Other organ involvement
  • Overall severity categories: mild/moderate/severe

References

  1. Thomas E, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE, Lerner KG, Glucksberg H, Buckner CD. Bone-marrow transplantation (first of two parts). N Engl J Med. 1975 Apr 17;292(16):832-43 link to original article PubMed
  2. Thomas ED, Storb R, Clift RA, Fefer A, Johnson L, Neiman PE, Lerner KG, Glucksberg H, Buckner CD. Bone-marrow transplantation (second of two parts). N Engl J Med. 1975 Apr 24;292(17):895-902 link to original article (contains staging scale) PubMed
  3. Rowlings PA, Przepiorka D, Klein JP, Gale RP, Passweg JR, Henslee-Downey PJ, Cahn JY, Calderwood S, Gratwohl A, Socié G, Abecasis MM, Sobocinski KA, Zhang MJ, Horowitz MM. IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol. 1997 Jun;97(4):855-64. link to original article PubMed
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