Post-transplant care

Early complications of HCT

Following hematopoietic cell transplantation (HCT), recipients will be immunocompromised and may also have treatment-related organ and tissue damage. Transplant recipients therefore require careful monitoring in the early post-transplant period to ensure that complications are recognized early, while there are more therapeutic options and while treatments can be more effective.

The most common complications that may occur in the early post-transplant period — from transplant infusion to one-year post-transplant — are listed below. Recognizing marrow transplant complications early is critical to the health of transplant recipients, and a timely collaboration with the transplant center to develop a treatment plan is recommended.

Because it is a complex disease with many manifestations, chronic graft-versus-host disease (GVHD) is discussed separately.

Oral mucositis is inflammation of oral mucosa that typically manifests as erythema or ulcerations. It can result from the cytotoxic effects of chemotherapy- and radiation-based pre-transplant conditioning regimens. [2,3]

Mouth sores associated with acute GVHD may also develop 2-4 weeks post-transplant. The severity and the patient's hematologic status govern appropriate oral management. Meticulous oral hygiene and palliation of symptoms are essential.
Acute GVHD is a common complication of allogeneic transplantation in which activated donor T cells attack the tissues of the transplant recipient after recognizing host tissues as antigenically foreign. The resulting inflammatory cytokines can cause tissue damage, and the commonly involved organs include the liver, skin, mucosa, and the gastrointestinal tract.

By classical definition, GVHD appearing before day 100 post-transplant is acute GVHD, and GVHD appearing after day 100 is chronic GVHD. However, acute GVHD may still occur later than 100 days post-transplant (e.g., during tapering of immunosuppressive drugs, or following a donor lymphocyte infusion). Some patients may also develop an overlap syndrome, where features of both acute and chronic GVHD are present. [4,5]
Graft failure is a rare, but life-threatening complication following allogeneic HCT. The most common cause of graft failure is an immunological rejection of the graft mediated by recipient T cells, natural killer cells, and/or antibodies. Other causes are infection, recurrent disease, or an insufficient number of stem cells in the donated graft. Graft failure occurs in approximately 5% of allogeneic transplants. [6]

The rate of failure can vary by graft source, and is increased in HLA-mismatched grafts, unrelated-donor grafts, T cell-depleted grafts, and umbilical cord blood grafts. Patients allo-sensitized through prior blood transfusions or pregnancy, and those receiving reduced-intensity conditioning are also at a higher risk of experiencing graft failure.

If graft failure occurs, treatment is a second HCT, using cells from the same donor or from a different donor. Patients experiencing graft failure after a cord blood transplant cannot get backup cells from the same cord blood unit. However, it may be possible to use a different cord blood unit or a backup adult donor instead.
All transplant recipients are susceptible to infections and require careful monitoring, which allows for timely administration of antibacterial, antiviral, and/or antifungal agents. [7]

Average times of full immune recovery are:
- Neutrophils and phagocytes: 1 month
- T cells: 6-12 months
- B cells: 12-24 months
Common infections in early and later post-transplant time periods are shown below.

> 0-3 Months
- Most bacteria
- Candida, Aspergillus, other fungi
- Herpes simplex
- Pneumocystis carinii
- Cytomegalovirus (CMV)
> 3 Months
- P. carinii
- Varicella-Zoster viruses
- Cytomegalovirus (CMV)
- Encapsulated bacteria
Organ injury and toxicity following transplant can include hepatic veno-occlusive disease (VOD) also known as sinusoidal obstruction syndrome, renal failure, pulmonary toxicity, thrombotic microangiopathy (TMA), and cardiovascular complications.

Pulmonary complications

In the early post-transplant neutropenic period, there is an increased risk of various bacterial, fungal, and viral infections of the lung, and pneumonia develops in 40% to 60% of transplant recipients. [8] The pneumonias that can occur include herpes simplex pneumonitis, cytomegalovirus pneumonitis, and Pneumocystis carinii pneumonia.

Bronchiolitis obliterans syndrome and bronchiolitis obliterans organizing pneumonia can appear later (post day 100) in the transplant recovery period. Bronchiolitis obliterans is closely associated with chronic GVHD and may result from alloimmunologic injury to host bronchiolar epithelial cells. [8,9]

Renal complications

Chronic kidney disease (CKD) is associated with the use of TBI in the transplant conditioning regimen, although many cases are idiopathic. TBI-associated CKD has a typical latency of 3-6 months from irradiation to injury. CKD after transplantation may not be recognized early due to competing clinical priorities such as the treatment of GVHD, and monitoring for infections and disease recurrence. [10]

Liver complications

Sinusoidal obstructive syndrome (SOS) also known as veno-occlusive disease (VOD) of the liver (SOS/VOD) is the result of damage to the hepatic sinusoids, resulting in biliary obstruction. Risk factors include the use of busulfan, TBI, infection, acute GVHD, and pre-existing liver dysfunction due to iron overload or hepatitis. [11]

Thrombotic microangiopathy

Transplant-associated TMA is a rare complication after allogeneic transplantation and can occur after autologous transplantation. Risk factors for TMA include pre-transplant conditioning with busulfan, fludarabine, platinum-based chemotherapy, and total body irradiation (TBI). TMA is also associated with the use of the calcineurin inhibitors, tacrolimus and cyclosporine. Transplant-associated TMA syndromes present as hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP). [12]

Cardiovascular complications

Cardiovascular complications may manifest as subclinical abnormalities or present as overt congestive heart failure or angina. The cardiac complications include any cardiac dysfunction due to cardiomyopathy, valvular anomaly, or conduction anomaly. [13]

Better clinical care has reduced mortality

After your patient leaves the transplant center and returns to your care, your support is critical to his or her long-term recovery and survival. Better clinical care and management of early post-transplant complications have led to significantly lower rates of transplant-related mortality (TRM) over time.

These post-transplant care guidelines were developed in partnership with leading transplant organizations and based on peer-reviewed publications. [14-19]

These free guidelines are accessible in multiple formats to meet your needs:

Long term screening
View early transplant complications and long-term screening and preventative practices to aid post-transplant treatment planning and patient management.
View screening guidelines
Vaccinations
Routine administration of vaccinations is vital for prevention of infectious complications. Access recommendations and timing for both autologous and allogeneic transplant recipients.
View vaccine schedule
GVHD screening
Easily identify and evaluate chronic graft-versus-host disease (GVHD) signs and symptoms with a thorough list of clinical manifestations and photos by area of the body.
View GVHD screening guidelines

References

NMDP^SM-facilitated transplants, 2016 analysis by CIBMTR®, the research program of NMDP.

Oral Complications of Chemotherapy and Head/Neck Radiation: Oral Mucositis. National Cancer Institute (PDQ database). Access

Keefe DM, Schubert MM, Elting LS, et al. Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer. 2007; 109(5): 820-831. Access

Martin PJ, Rizzo JD, Wingard JR, et al. First- and second-line systemic treatment of acute graft-versus-host disease: Recommendations of the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2012; 18(8): 1150-1163. Access

Flowers MED, Inamoto Y, Carpenter PA, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011; 117(11): 3214-3219. Access

Olsson R, Remberger M, Schaffer M, et al. Graft failure in the modern era of allogeneic hematopoietic SCT. Bone Marrow Transplant. 2013; 48(4): 537-543. Access

Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: A global perspective. Biol Blood Marrow Transplant. 2009; 15(10): 1143-1238. Access

Yen KT, Lee AS, Krowka MJ, Burger CD. Pulmonary complications in bone marrow transplantation: a practical approach to diagnosis and treatment. Clin Chest Med. 2004; 25(1): 189-201. Access

Yoshihara S, Yanik G, Cooke KR, Mineishi S. Bronchiolitis obliterans syndrome (BOS), bronchiolitis obliterans organizing pneumonia (BOOP), and other late-onset noninfectious pulmonary complications following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2007; 13(7): 749-759. Access

Cohen EP, Pais P, Moulder JE. Chronic kidney disease after hematopoietic stem cell transplantation. Semin Nephrol. 2010; 30(6): 627-634. Access

Laskin BL, Goebel J, Davies SM, Jodele S. Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Blood. 2011; 118(6): 1452-1462. Access

Ho VY, Cutler C, Carter S, et al. Blood and Marrow Transplant Clinical Trials Network Toxicity Committee Consensus Summary: Thrombotic microangiopathy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005; 11(8): 571-575. Access

Tichelli A, Bucher C, Rovó A, et al. Premature cardiovascular disease after allogeneic hematopoietic stem-cell transplantation. Blood. 2007; 110(9): 3463-3471. Access

Majhail NS, Rizzo JD, Lee SJ, et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation; Center for International Blood and Marrow Transplant Research (CIBMTR), American Society for Blood and Marrow Transplantation (ASBMT), European Group for Blood and Marrow Transplantation (EBMT), Asia-Pacific Blood and Marrow Transplantation Group (APBMT), Bone Marrow Transplant Society of Australia and New Zealand (BMTSANZ), East Mediterranean Blood and Marrow Transplantation Group (EMBMT) and Sociedade Brasileira de Transplante de Medula Ossea (SBTMO). Co-published in Biol Blood Marrow Transplant, 2012, 18(3): 348-371; Bone Marrow Transplant, 2012, 47(3): 337-341; and Hematol Oncol Stem Cell Ther, 2012, 5(1): 1-30. Access

Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: A global perspective. Biol Blood Marrow Transplant. 2009; 15(10): 1143-1238. Access

Ljungman P, Cordonnier C, Einsele H, et al. Vaccination of hematopoietic cell transplant recipients. Bone Marrow Transplant. 2009; 44(8): 521-526. Access

Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Response Criteria Working Group Report. Biol Blood Marrow Transplant. 2015; 21(3): 389-401.

Lee SJ, Wolff D, Kitko C, et al. Measuring therapeutic response in chronic graft-versus-host disease. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2014 Response Criteria Working Group Report. Biol Blood Marrow Transplant. 2015; 21(6): 984-999.

These guidelines have been developed by the NMDP in consultation with Sandra A. Mitchell, CRNP, MScN, AOCN; National Institutes of Health Clinical Center; and Steven Z. Pavletic, M.D.; National Cancer Institute, National Institutes of Health, Bethesda, Md. The information in this document does not represent the official position of the NIH or the U.S. Government.

Post-transplant care

Early complications of HCT

Better clinical care has reduced mortality

Long term screening

Vaccinations

GVHD screening

References

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Post-transplant care

Early complications of HCT

Oral mucositis

Acute graft-versus-host disease

Stem cell graft failure

Early infections

Organ injury/toxicity

Better clinical care has reduced mortality

Long term screening

Vaccinations

GVHD screening

References