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Chronic graft-versus-host disease and late effects after hematopoietic stem cell transplantation
1Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Insights
Late effects after hematopoietic stem cell transplant (HSCT) stem from the transplant process or preparative regimen. These can include immune issues like chronic graft-versus-host disease (GVHD) and endocrine, ocular, pulmonary, or bone problems, plus secondary cancers.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for various hematologic and oncologic conditions.
- Late effects following HSCT can significantly impact long-term patient outcomes and quality of life.
- These effects are broadly categorized into those related to the transplant process and the preparative regimen.
Purpose of the Study:
- To comprehensively review the spectrum of late effects occurring after HSCT.
- To detail the common manifestations, risk factors, and management strategies for these late effects.
- To emphasize the importance of lifelong surveillance for HSCT survivors.
Main Methods:
- Literature review and synthesis of existing data on late effects post-HSCT.
- Categorization of effects based on their origin (transplant process vs. preparative regimen).
- Summary of clinical presentations, diagnostic considerations, and therapeutic approaches.
Main Results:
- Transplant process-related effects include immune system recovery delay and chronic graft-versus-host disease (GVHD), affecting skin, mouth, liver, GI tract, and eyes.
- Preparative regimen-related effects encompass endocrine deficiencies (GH deficiency, hypothyroidism, diabetes), cataracts, pulmonary issues (bronchiolitis obliterans), decreased bone mineral density, and secondary malignancies.
- Chronic GVHD management involves prolonged immunosuppression, while endocrine deficiencies require hormone supplementation. Bone density issues are managed with lifestyle changes and medication.
Conclusions:
- Late effects of HSCT are diverse and require vigilant, long-term monitoring.
- Early recognition and appropriate management of these complications are crucial for improving survival and quality of life in HSCT recipients.
- Lifelong follow-up is essential for all HSCT survivors to detect and manage potential delayed adverse events.
Abstract:
Late effects following HSCT are related to either the transplant process or to the transplant preparative regimen. Problems related to the transplant process include delayed recovery of the immune system and chronic GVHD. Chronic GVHD presents between 3-14 months post-HSCT in approximately 20% of matched sibling transplants and 40% of matched unrelated donor recipients. Most commonly involved sites are skin, mouth, liver, gastrointestinal tract, and eye. Patients with platelet count < 100,000/ml and receiving cortocosteroid therapy at day 80 with any clinical manifestations of chronic GVHD require prolonged immune suppressive therapy with prednisone, cyclosporine +/- other agents. Treatment should be administered until all clinical and pathological signs and symptoms of chronic GVHD have resolved which may take one to several years. Problems related to the transplant preparative regimen include those involving the endocrine system, eyes, lungs, bone, and development of secondary malignancies. Endocrine deficiencies include growth failure with growth hormone (GH) deficiency, overt hypothyroidism, primary gonadal failure, Type 1 or Type 2 diabetes, and exocrine pancreatic insufficiency. These problems develop at any time post-HSCT, but usually occur within the first few years and should be treated with appropriate hormone supplementation. Eye problems are primarily related to development of cateracts secondary to total body irradiation (TBI) or prolonged corticosteroid use. Cateracts developing after fractionated frequently do not require removal. Pulmonary problems may be due to bronchiolitis obliterans (BO) or to restrictive lung disease. BO may be associated with chronic GVHD and may respond to chronic GVHD therapy. Restrictive lung disease does not occur for many years after HSCT. There is not therapy for this problem. Development of decreased bone mineral density (BMD) is related to GH deficiency and/or corticosteroid therapy. Treatment includes withdrawal of corticosteroids, administration of GH and calcium, Vitamin D and antiresorptive agents. All malignant disease survivors are at risk for development of secondary malignancies, including survivors of HSCT. Recipients of TBI are at highest risk as are children. All pediatric and adult survivors of HSCT should be followed for their life-time for development of delayed effects of transplantation.