INTRODUCTION:

The only curative therapy for many of the hematological disorders as well as immune deficiency disorders, inborn errors of metabolism, genetic disorders and some of the solid tumors is allogeneic stem cell transplantation. Despite advances in HLA typing, GvHD intensive prophylaxis and post transplant immunosuppressive therapy, GvHD remains a major complication of concern attributing to transplant related mortality.

aGvHD occurs when the transplanted donor T lymphocytes recognize antigenic disparities between the host and recipient. Inflammatory cytokine release has been implicated as the primary mediator of aGvHD and activation of T cells is one step in the complex process. Deregulated cytokine release by cells other than T cells leads to tissue damage associated with aGvHD.¹ aGvHD predisposes to multi-organ syndromes of tissue inflammation and or fibrosis that primarily affect skin, gastrointestinal tract, liver and mucosal surfaces. Clinically, GvHD is described as acute GvHD when it occurs within 100 days after Hematopoietic Stem Cell Transplantation (HSCT) or chronic GvHD which occurs after 100 days, but these syndromes may overlap in time.

Epidemiology:

Acute GvHD is the second leading cause of death, after disease relapse following allogeneic HSCT.² The exact incidence of aGvHD after allogeneic HSCT is unknown. Reported incidence rates range from 9 to 50% in patients who undergo allogeneic HSCT from a genotypically HLA identical sibling. Acute GvHD is also common in matched unrelated donors and in haplo identical related donors.³With matched related and unrelated donors, the cumulative incidence of acute GvHD remains approximately 40-60% respectively.⁴ It has been estimated that 20-50% of all transplanted patients experience grade 2 or more aGvHD despite immuno-suppressive prophylaxis.¹

Risk factors:

The risk factors of aGvHD are multifactorial and have been studied intensively over the last three decades. These include:

· Human leukocyte antigen (HLA) disparity

· Increased age in donor and recipient

· Multiparous female donor

· Donor and recipient sex mismatch

· Increased dose of total-body irradiation(TBI)

· Full intensity conditioning regimen

· Ineffective acute GvHD prophylaxis

· Source of the graft/unrelated donor

· Lack of protective environments

· Splenectomy

· Immunoglobulin use

· Pre transplant comorbidities

· ABO compatibility

· Prior exposure to Herpes viruses

· Donor transfusions

· Performance score

· Antibiotic gut decontamination

· Post-transplant transfusion

Further, acute GvHD also differs by disease, Acute leukemia compared with other hematologic malignancies is a significant risk factor for aGvHD.^5,3 Certain cellular markers in donor grafts, most notably, the T cell subsets expressing IL-7 receptor-α (CD127) and PD-1 and elevated levels of tumor necrosis factor-α in both graft and patient before HSCT posed risk of aGvHD development.⁶ Transplantation with an identical sibling donor and the use of ATG in the conditioning regimen containing TBI have been associated with a decreased risk of grades II–IV aGvHD.⁷

Classification:

GvHD is sub classified based on the timing of presentation and the features present as follows:

· Classic acute GvHD: Cases present within 100 days of HSCT and display features of aGvHD. Diagnostic and distinctive features of chronic GVHD are absent.

· Persistent, recurrent, late onset acute GvHD: Cases present greater than 100 days post-HSCT with features of aGvHD. Diagnostic and distinctive features of chronic GvHD are absent

· Classic chronic GvHD: Cases may present at any time post-HCT. Diagnostic and distinctive features of chronic GvHD are present. There are no features of acute GvHD.

· Overlap syndrome: Cases may present at any time post-HSCT with features of both chronic GvHD and acute GvHD. On occasion, this is colloquially referred to as "acute on chronic" GvHD.⁸

Pathophysiology:

GvHD occurs as the donor cells are not identical with the recipient (patient) cells. This leads to a fight between the T cells of the donor and the host immune system. Development aGvHD involves 3 phases as shown below (Fig 1). Donor T lymphocytes play the crucial role of mediating GvHD following interactions with activated host and donor antigen-presenting cells (APC). A complex network of cytokines, chemokines, cellular receptors and immune cell subsets then modulate T-cell/APC interactions that result in GvHD.⁹ The inflammatory cascade and continued tissue damage can lead to release of biomarkers of aGvHD into the circulation even before the onset of clinical signs of GvHD potentially predicting therapy responses. These biomarkers include soluble CD30 from activated T cells, elafin (skin-specific), regenerating islet-derived 3-α (REG3α;gut-specific), suppressor of tumorigenicity 2 (ST2; a member of the IL-1 receptor family–binding IL-33), microRNA and others.¹⁰ As counterparts to the effector cells, the T regulatory cells (T reg) suppress GvHD and also impairs the target tissue homing of effector cells.¹

Table 2: Grading of aGvHD²

Overall clinical grade	Lower GI	Upper GI	Liver	Skin
I	0	0	0	1-2
II	1	1	1	3
III	2-3		2-4	-
IV	4		-	4

Clinical manifestations:

Clinical manifestations of aGvHD include specific derangements in the skin, liver and gastrointestinal tract, occasionally the eyes and oral mucosa. It often presents with skin rash, diarrhea, elevated bilirubin, and it is associated with recurrent infections.

Acute Skin GvHD:

Characterised by maculopapular rash, sometimes pruritic or painful. Typically distributed on the palm of the hands and soles of the feet, later progresses to the face, neck, upper chest and trunk. Stage III shows generalized erythroderma with bullae formation and desquamation of the epidermal layers of the skin.

Acute liver GvHD:

Characterized by an isolated hyperbilirubinemia. The increase in alkaline phosphatase is seen more frequently than liver enzyme abnormalities.

Acute Gastrointestinal GvHD:

Exhibit profuse diarrhea with anorexia and sometimes nausea. Progression with abdominal pain, GI bleeding and ileus is associated with later stages of GvHD¹

The most common target organ of aGvHD is the skin, followed by the gastrointestinal tract.⁷The mortality risk varies depending on the stage and grade of aGvHD²

Diagnosis:

Diagnosis of aGvHD can be made as follows:

· Clinically in patients presenting with a rash, diarrhea and elevation of bilirubin within the first several weeks of transplant.

· Skin and liver biopsies

· Plasma biomarkers: IL-2-receptor-a, TNF receptor-1, IL-8 and hepatocyte growth factor has been suggested as a confirmatory tool for the diagnosis of aGvHD at the onset of clinical symptoms and to provide prognostic information independent of GvHD severity.²

Management:

Treatment should be tailored based on the severity of presentation and symptom management. Calcineurin inhibitors are the cornerstone of prophylaxis, while steroids remain the gold standard of treatment.⁴

· Methyl Prednisolone (Systemic corticosteroid) is given at 2mg/kg/day given in 2 divided doses in grade III-IV, while 0.5 to 1mg/kg/day for grade II disease.

· The original immune suppressive prophylaxis must be continued. Median time to resolution of aGvHD is 30-42 days.

· In patients who respond to initial therapy, short-term tapering treatment with prednisone to a cumulative dose of 2,000mg/m² is effective and expected to minimize steroid-related complications.

· In steroid refractory cases, alternative therapies include antithymocyte globulin (ATG), cyclosporine, mycophenolate mofetil, anti-IL-2 receptor, anti-CD5-specific immunotoxin, pan T-cell ricin A-chain immunotoxin, ABX-CBL, etarnercept, infliximab, daclizumab, vilizumab and pentostatin. These agents can be used alone or in combination.

· The use of mesenchymal stem cell in steroid-refractory aGvHD is found to be useful for patients with lower grade aGvHD with only skin involvement. Extracorporeal photopheresis also shows promise as a less immunosuppressive strategy to reduce rates of aGvHD.²

Prevention:

Prevention of aGvHD is the most vital dimension in patients undergoing allogeneic HSCT. Prophylaxis is mainly based on immunosuppression achieved either by T cell depletion or pharmacologically. The most commonly used GvHD prophylaxis following full intensity conditioning regimen includes a Calceneurin Inhibitor (e.g. Cyclosporine, Tacrolimus) with Methotrexate or MMF. Recently, Sirolimus which is a commonly used immunosuppressant in solid organ transplantation is also used for GvHD prophylaxis.²Several studies support that combination of sirolimus and tacrolimus promoted rapid engraftment, lowered acute GvHD incidence, reduced transplant-related toxicity and improved survival.¹¹

Prognosis:

The overall survival at one year is about 20-30%.Corticosteroid-refractory aGvHD has a poor prognosis and the second-line therapies have high failure rates.¹²

· Patients with moderate to severe GvHD have a significantly higher mortality rate compared with those with mild disease. Estimated five-year survival rates of patients with grade III (C) and grade IV (D) acute GvHD are 25 and 5 percent, respectively.

· Patients with the same grade but different patterns of skin, gut or liver involvement often have significantly different outcomes. As an example, a patient with stage IV cutaneous GvHD alone would be expected to have a much more favorable outcome than a patient with stage IV gastrointestinal GvHD alone, although both have overall grade IV GvHD.¹³

Nursing Management of a patient with Acute GVHD:

Nursing management in Acute GvHD is discussed using a case report and nursing process approach

Case Report:

Baby A., a 4 year old is the only daughter of an affluent non consanguineous parents in Uganda. She was evaluated in her home town for fever at 1 year of age and was diagnosed to have Sickle cell Anemia. She also developed recurrent painful bony crisis and severe back ache for 3 years with several episodes of upper respiratory tract infection within 3 months for which she was repeatedly treated with antibiotics and blood transfusion. In view of these complaints Baby A. was referred to a tertiary care hospital in India for definitive management. On examination, child looked pale, had hepatomegaly of 2 cm below the right costal margin. Had no icterus, cyanosis, clubbing, peripheral lymphadenopathy or splenomegaly. Her mutation analysis confirmed Homozygous Sickle cell Anemia, Hemoglobin was 8.9g%, Liver function tests were elevated (Blirubin-2.47mg/dl, SGOT-62U/L), Serum Ferritin was 439ng. Ultrasonography of abdomen revealed small ringed spleen. MRI brain suggested subtle focal changes of right terminal Internal Carotid artery. Cardiac, dental and ENT clearance was obtained as part of transplant work up. Due to unavailability of sibling donor and matched unrelated donor, Baby A. underwent Haplo-identical Allogeneic Stem Cell Transplantation with her mother being the donor (32 years).

Conditioning regimen protocol: she received the following condition regimen and tolerated them without any complications:

· Inj. Thiotepa 8mg/kg on day -6 (155mg)

· Inj. Treosulfan 14gm/m2/day on day -5, -4 (10gm) to day -3 (13gm)

· Inj. Fludarabine 40mg/m2/day from day -5, -4, -3 (30 mg) to day-2 (33mg)

· Inj. Rituximab 375mg/m2 (300mg) on day-1

· Total Body Irradiation (200cGy) on day -1

After alpha beta T cell depletion, 190ml of Stem cell product with CD 34 cell dose of 10.2 x10⁶ cells/Kg was infused. No immediate complication was noted during the infusion. She achieved complete chimerism status on Day 28. Post HSCT, she developed Febrile Neutropenia from day +12 and multiple infections (Day+33: Enterococcus faecium and Klebsiella Pneumonia CRO Sepsis). She received Inj. Amikacin 340mg od, Inj. Meropenem 750mg Q8h, Inj. Colistin 2.5 MU Q8h, Inj. Teicoplanin 200mg Q12h, Inj. Metronidazole 150mg and was on Ionotropic support. For fungal pneumonia she was managed with Inj. Amphotericin B 50mg od and Inj.Caspofungin 35mg bd. On day +4, she developed Grade II mucositis which was managed with Total Parenteral Nutrition and opioid analgesics infusion. Mucositis improved as the Neutrophil Engraftment occurred. Child also developed BK virus and Adeno virus infection inspite of the prophylaxis with Tab. Leflunamide 100mg and Inj. Ciprofloxacin 100mg bd. Hence, she received Inj. Cidofovir 75mg (once a week). She developed severe painful oral ulcers on day +48 due to Herpes simplex virus 1 and was given Inj. Acyclovir 10mg/kg for 16 days.

In addition to the T cell depleted stem cell infusion, Inj. Cyclosporine 480mg bd was given additionally to prevent GvHD. Child started showing symptoms of acute Gastro intestinal GvHD since day +12 with progressively worsening symptoms from grade II to grade IV disease presenting with diarrhoea, abdominal distention, pain, paralytic ileus, and hematochezia. She was initially managed with Inj. Methyl prednisalone 18mg IV and Inj. Octreotide 100mcg od. On day +41 and day +65, she received 2 doses of CD 45 RO cells (3.7 x10⁶ cell/kg) reinfusion from the cryopreserved donor samples. She also received IVIG 400mg/kg (10g) on day +7, +24, +29. Inj. Cyclosporine was stopped as she developed symptoms of cyclosporine induced Posterior Reversible Encephalopathy Syndrome (PRES). She was on low dose of Tacrolimus 0.25mg bd. Inj. Methyl prednisalone was tapered and stopped as she developed steroid refractory Gastro intestinal GvHD. Inj. Ruxolinitib 5mg was given od, Inj. Basiluximab 20mg IV was given once a week. She was on nil per oral status on Total Parenteral Nutritional support. On day +100, she was able tolerate feeds. She got discharged from the hospital on day +191 during which, she was asymptomatic, ambulant and on oral diet. She is followed up in out-patient basis once in 3 months and subsequently every 6 months. Her day +60 and day +90 chimerism status was complete.

NURSING CARE:

1. Nursing diagnosis:

Actual infection related to immunosuppression secondary to myeloablative chemotherapy, total body irradiation, Probable fungal pneumonia, Enterococcus faecium sepsis, Klebsiella pneumonia CRO sepsis, adeno virus, BK virus positive status

Expected outcome: Infection is minimised as evidenced by normothermia, negative blood surveillance culture, normal chest radiograph, ANC >1500mm³

Nursing interventions

· Inspected for signs of infection including fever, chills, vomiting, diarrhea, cough. WBC mm³. Developed fever of 101⁰ F on day +1 which was managed with Managed with Inj. Meropenem and Inj. Amikacin.

· Developed high grade fever, flushing and diarrhoea on day +11, +16 with signs of septic shock. On day +33, developed a breakthrough high grade fever, High resolution CT revealed left lobe superior segment consolidation. Day +50, blood culture revealed Enterococcus faecium sensitive to Teicoplanin, Carbopenemase resistant Klebsiella pneumonia sensitive to Colistin and Teigicyclin. Inj. Teicoplanin, Inj. Colistin and Inj. Caspofungin, Inj. Metronidazole, Inj. Liposomal Amphotericin B, Ionotropic support

· Monitored the central venous access device site for infection and performed weekly dressing meticulously. Hickmann’s catheter was removed on day +56

· Obtained chest X ray, cultures and sensitivities,

· Regularly monitored (twice a week) for Blood CMV and urine BK virus reactivation. Started on Tab. Leflunamide and Inj. Ciprofloxacin (CMV and BK virus prophylaxis)

· Day +33 developed asymptomatic BK viruria with quantitative viral load of 10.33 log. Received Inj. Cidofovir 75mg (once a week). On Day +41 adenovirus PCR became positive. Day +75, developed high viral load (Log 7.31), restarted Inj. Cidofovir (4 doses). Developed several painful oral ulcers at the tongue, floor of mouth and palate. Day +48: Tissue scraping from oral ulcers revealed HSV 1 Viral PCR was positive (Inj. Acyclovir10mg/kg for 16 days)

· Adopted reverse barrier nursing technique (protective isolation)

· Ensured vigorous hand washing. Maintained aseptic technique while performing procedures. Taught on prevention of infection

· Practiced meticulous oral/ body hygiene

· Instituted low microbial diet with high calories, proteins, vitamin C, minerals and fluids

· Administered antimicrobial therapy:

Evaluation:

Infection was minimised. Patient had negative blood culture report. Afebrile. Had clear lung sounds. WBC-6100/cumm. Day +43, BK virus load became negative. Tzanck smear was negative.

2. Nursing diagnosis:

Ineffective protection related to Myelosuppression secondary to chemotherapy/total body irradiation, Gastro intestinal GvHD, post transplant immunosuppressive therapy, drug injury (prolonged antimicrobial therapy), nutritional deficiencies.

Expected outcome:

Patient achieves optimal body functioning as evidenced by improvement in Gastro intestinal GvHD, general health status and absence of treatment related complications.

Nursing interventions:

· Monitored vital signs

· Assessed for post stem cell transplant complications:

· Observed for signs and symptoms of pancytopenia/ myelosuppression. Monitored complete blood counts.

· Administered blood products(Irradiated packed red cells:20, Irradiated platelet rich concentrates:6, fresh frozen plasma:7) and granulocyte colony stimulating factor 50mcg 3/7.

· Monitored for side effects of chemotherapy, radiation, antimicrobial therapy such as nausea, vomiting, bone marrow suppression, diarrhoea, alopecia and infection.

· Assisted in rectal biopsy. Administered steroids and immunosuppressants.

On day +11 administered Inj. Cyclosporine in addition to alpha beta T cell depletion of stem cells. On day +12 she developed Diarrhoea, Rectal biopsy showed Gastro intestinal GvHD grade 1. Was started on Inj. Methyl Prednisalone 18mg IV od (+13) to bd (+15). Diarrhea worsened on day+17(Grade III GvHD). Started on Inj. Cyclophosphamide 475mg (25mg/kg), Inj. Etanercept 7mg S/C od twice a week, Oral Budesonide

· Assessed the nutritional status. Kept her on nil per oral status. NG tube to dependent drainage. Provided parenteral nutrition

· Day +19 she developed cyclosporine induced Posterior Reversible Encephalopathy Syndrome. Hence Cyclosporine was stopped.

· Day +23 diarrhoea persisted Inj. Octreotide infusion was started. Day+30 started on low dose Tacrolimus (0.25mg bd). Tapered Methyl prednisolone as she developed steroid refractory Grade IV GvHD.

· Day +45 she developed abdominal distention and pain suggestive of paralytic ileus.

· Inj. Ruxolinitib (Jakafi) 5mg and Inj. Basiluximab 20mg IV once a week was given as she developed hematochezia.

Evaluation:

There was marked improvement in GvHD. Infection was controlled.WBC mm³ Vital signs were stable. Chimerism was complete on day+28, +60, +90. Was able to tolerate oral food

3. Nursing diagnosis:

Diarrhoea related to Grade IV Gastro intestinal GvHD, side effects of conditioning regimen and antibiotic/ drug intolerance

Expected outcome:

Diarrhoea is controlled as evidenced by patient passing soft, formed stool not more than thrice a day

Nursing interventions:

· Checked bowel sounds, observed for abdominal distention, rigidity and pain

· Observed the stool pattern, recorded frequency, character and volume. Had severe abdominal pain, loose stools and hematochezia.

· Monitored vital signs for deficient fluid volume

· Obtained stool specimen for culture and sensitivity. Assisted for rectal biopsy to rule out Gastro intestinal GvHD grading. Rectal biopsy revealed evidence of grade IV Gastro intestinal GvHD

· Administered Oral Rehydration Solution after each episode of loose stools

· Administered IV fluids. Monitored intake output chart.

· Administered parenteral nutrition, steroids and antibiotics for GvHD management

Evaluation:

Patient passed soft formed stool. There was complete improvement in Gastro intestinal GvHD. On day +100 child was able to tolerate oral feeds.

4. Nursing diagnosis:

Impaired oral mucosal membrane related to side effects of chemotherapy/ total body irradiation

Expected outcome:

She achieves optimal integrity of the oral mucosal membrane as evidenced by absence of mucositis

Nursing interventions:

· Assessed the oral mucous membrane. Had painful oral ulcers (Grade II oral mucositis)

· Kept on NPO status, administered Total Parenteral Nutrition

· Administered opioid analgesics

· Encouraged mouth wash using diluted 7% Sodium bicarbonate followed by 2% Chlorhexidine solution 4 times/day as the mucositis improved

· Encouraged GvHD diet once tolerant to oral diet

· Encouraged 2-3 litres of water/day

Evaluation:

Grade 2 oral mucositis completely resolved as the neutrophil engraftment occurred. She was able to tolerate normal diet.

5. Nursing diagnosis:

Imbalanced nutrition less than body requirement related to grade IV Gastro intestinal GvHD, side effects of conditioning regimen, malabsorption of nutrients, increased metabolic rate secondary to fever/infection

Expected outcome:

Patient achieves optimal nutritional status and protein stores as evidenced by adequate calorie intake based on body requirement and weight gain

Nursing interventions:

· Determined specific causes for imbalanced nutrition. Auscultated for bowel sounds. Assessed the nutritional status

· Monitored lab values: Hb- 8.9g%, WBC-6100/cumm, serum Ferritin-439 ng%, total protein-6.9g/dl, albumin-4.3g/dl

· Evaluated the effectiveness of antiemetic and antidiarrheal therapy

· Assessed her food preferences

· Administered parenteral nutrition and intravenous fluids

· Implemented GvHD diet after maintaining NPO status

· Implemented meticulous oral hygiene with 2% chlorhexidine solution Q4 hourly

Evaluation:

Child’s nutritional status gradually improved. Parenteral nutrition was stopped. Paralytic ileus symptoms resolved. She was able to tolerate oral feeds from day +100. There was significant weight gain.

6. Nursing diagnosis:

Fatigue related to decreased oxygen carrying capacity of blood, NPO status, pain, side effects of chemotherapy/ radiation, hyperthermia, infection

Expected outcome:

Child attains optimal energy and activity tolerance as evidenced by ability to play and perform her ADLs

Nursing interventions:

· Assessed the level of fatigue and the specific causes of fatigue

· Assisted in planning the ADLs, prioritized the activities with the parents

· Encouraged frequent rest periods after activity

· Transfused blood when haemoglobin was less than 8g%. She received 20 units of Irradiated Packed red cells during the peri transplant period

· Encouraged high protein, high calorie diet. Administered total parenteral nutrition

· Instituted supplemental oxygen therapy(2- 4litres)

· Administered antipyretics(Inj. Febrinil 250mg prn) and antibiotics/ antifungal and antiviral medications

Evaluation:

There was improvement in child’s energy level. She was able to perform ADLs and play actively.

7. Nursing diagnosis:

Anxiety (Parental) related to high risk procedure, uncertainty of treatment outcome and hospitalization

Expected outcome:

Anxiety is minimised as evidenced by adopting positive coping mechanisms and restful appearance

Nursing interventions:

· Acknowledged awareness of the parent’s anxiety. Examined anxiety provoking situations

· Reassured and provided a non-threatening environment

· Oriented them to new experiences, procedures and people in the Bone marrow transplant Unit

· Involved patient in play therapy

· Encouraged verbalization of feelings and cleared their doubts in simple language

Evaluation:

Anxiety was minimised. Parents were restful and calm. They verbalised familiarity over the environment and procedure

8. Nursing diagnosis:

Knowledge deficit regarding disease process, procedures and treatments in hematopoietic stem cell transplantation, complications, home care and follow up related to lack of information

Expected outcome:

Learning needs are met regarding disease process, procedures and treatments in hematopoietic stem cell transplantation, complications, home care and follow up as evidenced by verbalization of understanding by parents

Nursing interventions:

· Assessed the parent’s level of knowledge and understanding of disease process, procedures, treatment plan and follow up after discharge

· Explained on Sickle cell anemia, haplo-identical allogeneic stem cell transplantation including harvest procedure, conditioning, engraftment, side effects, complications including GvHD and the physical set up of bone marrow transplantation unit

· Explained the need for infection control, care of central venous access device, antiobiotic/ antifungal/ antiviral therapy, low microbial diet, total parenteral nutrition and blood transfusion.

· Discussed on follow up schedule and home care

Evaluation:

Parents verbalised understanding and confidence in caring for Baby A.

CONCLUSION:

aGvHD highlights the need for appropriate risk reduction while HSCT planning, patient tailored prophylaxis, prompt assessment and monitoring, early detection aid to appropriate management and expected treatment outcome. There is a tremendous role of hematology nurse while caring for patients with aGvHD.

CONFLICT OF INTEREST:

The authors have declared no conflicts of interest.

REFERENCE:

1. Ball LM, Egeler RM. Acute GvHD: pathogenesis and classification. Bone Marrow Transplantation. 2008 Jun; 41(2): S58–64.

2. Nassereddine S, Rafei H, Elbahesh E, Tabbara I. Acute Graft Versus Host Disease: A Comprehensive Review. Anticancer Res. 2017 Apr 1; 37(4): 1547–55.

3. Lee S-E, Cho B-S, Kim J-H, Yoon J-H, Shin S-H, Yahng S-A, et al. Risk and prognostic factors for acute GVHD based on NIH consensus criteria. Bone Marrow Transplant. 2013 Apr; 48(4): 587–92.

4. Gooptu M, Koreth J. Better acute graft-versus-host disease outcomes for allogeneic transplant recipients in the modern era: a tacrolimus effect? Haematologica. 2017 May; 102(5): 806–8.

5. Hahn T, Mc Carthy PL, Zhang M-J, Wang D, Arora M, Frangoul H, et al. Risk Factors for Acute Graft-Versus-Host Disease After Human Leukocyte Antigen–Identical Sibling Transplants for Adults With Leukemia. J Clin Oncol. 2008 Dec 10; 26(35): 5728–34.

6. Stikvoort A, Gaballa A, Solders M, Nederlof I, Önfelt B, Sundberg B, et al. Risk Factors for Severe Acute Graft-versus-Host Disease in Donor Graft Composition. Biology of Blood and Marrow Transplantation. 2018 Mar 1; 24(3): 467–77.

7. Wang F, Cai B, Wang L, Gu Z, Luo L, Wei H, et al. Risk Factors for Acute Graft-Versus-Host Disease After Allogeneic Haematopoietic Stem Cell Transplantation: A Single-Center Experience. Med Sci Monit. 2017 Feb 3; 22: 58–65.

8. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec; 11(12): 945–56.

9. Murray J, Stringer J, Hutt D. Graft-Versus-Host Disease (GvHD) [Internet]. The European Blood and Marrow Transplantation Textbook for Nurses: Under the Auspices of EBMT [Internet]. Springer; 2017 [cited 2020 Jun 3]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK543657/

10. Holtan SG, Pasquini M, Weisdorf DJ. Acute graft-versus-host disease: a bench-to-bedside update. Blood. 2014 Jul 17; 124(3): 363–73.

11. Choi SW, Levine JE, Ferrara JLM. Pathogenesis and Management of Graft versus Host Disease. Immunol Allergy Clin North Am. 2010 Feb; 30(1): 75–101.

12. Funke VAM, Moreira MCR, Vigorito AC, Funke VAM, Moreira MCR, Vigorito AC. Acute and chronic Graft-versus-host disease after hematopoietic stem cell transplantation. Revista da Associação Médica Brasileira. 2016 Oct; 62: 44–50.

13. Cahn J-Y, Klein JP, Lee SJ, Milpied N, Blaise D, Antin JH, et al. Prospective evaluation of 2 acute graft-versus-host (GVHD) grading systems: a joint Société Française de Greffe de Moëlle et Thérapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI), and International Bone Marrow Transplant Registry (IBMTR) prospective study. Blood. 2005 Aug 15; 106(4): 1495–500.

Received on 29.06.2020 Modified on 08.08.2020

Asian J. Nursing Education and Research. 2020; 10(4):521-528.

DOI: 10.5958/2349-2996.2020.00113.5

Clinical stage	Lower GI	Upper GI	Liver (Bilirubin level in mg/dl)	Skin (% rash of body surface area)
1.	Diarrhea <500 ml/day	Nausea/vomiting	2-3	<25%
2.	Diarrhea 500-1000 ml/day		3-6	25-50%
3.	Diarrhea 1000-1500 ml/day		6-15	>50% Generalized erythroderma
4.	Diarrhea >1500ml/day		>15	Bullae/ desquamation