Seminars in Hematology
Volume 49, Issue 1 , Pages 1-3, January 2012

How Can We Improve Life Expectancy and Quality of Life in Long-Term Survivors After Allogeneic Stem Cell Transplantation?

Long Term Transplant Clinic (LTTC), Hematology and Stem Cell Transplantation Section, Vanderbilt University Medical Center, Nashville, TN

Article Outline

 

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides curative therapy for a variety of diseases. Over the past several decades, significant advances have been made in the field of allo-HSCT and now allo-HSCT has become an integral part of treatment modality for a variety of hematologic malignancies and some nonmalignant diseases. The development of less toxic pretransplant conditioning regimens, more effective prophylaxis of graft-versus-host- disease (GVHD), improved infection control, and other advances in transplant technology have resulted in a rapidly growing number of transplant recipients surviving long-term free of the disease for which they were transplanted.

These patients have increased risks for a variety of late complications, which can cause morbidity and mortality.1, 2, 3, 4, 5, 6 Most long-term survivors return to the care of their local hematologists/oncologists or primary care physicians, who may not be familiar with specialized monitoring recommendations for this patient population. As allo-HSCT survivorship increases, the focus of care has shifted to the identification and treatment of long-term complications that may affect quality of life. Preventive care as well as early detection and treatments are important aspects to reducing morbidity and mortality in long-term survivors after allo-HSCT.7 This issue of Seminars in Hematology focuses on the essential knowledge about diagnosis, screening, treatment, and long-term surveillance of long-term survivors after allo-HSCT.

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Numbers of Long-Term Survivors are Growing 

Since the first three cases of successful allo-HSCT in 1968, the number of allo-HSCTs performed annually has increased steadily over the past three decades.8, 9, 10, 11 The number of HSCTs performed annually increases every year and more than 30,000 allo-HSCTs are expected to be performed worldwide in 2011. With broadening indications, more options for allo-HSCT and improvement in survival, by 2020 there may be up to half a million long-term survivors after allo-HSCT worldwide. Advances in HSCT practice and supportive care have led to improved outcomes and increasing number of long-term HSCT survivors.

Historically, the limitation of allo-HSCT has been transplant-related mortality (TRM). In order to offer the curative allo-HSCT treatment option in most patients, safer regimens with acceptable GVHD associated morbidity and TRM are preferred. A recently published M. D. Anderson Cancer Center study showed an excellent overall and progression-free survival (85% and 83%, respectively, after median follow-up of 60 months) for relapsed follicular lymphoma after fludarabine, cyclophosphamide, and rituximab (FCR) RIC allo-HSCT.12 In this era, a stem cell source can be found for virtually all patients who have an indication to receive allo-SCT. Since 2007, more allo-HSCT procedures have been performed using alternative donor stem cell sources, such as volunteer unrelated donors or cord blood, rather than related donors.10, 11 RIC haploidentical-related donor or cord blood transplantations have emerged as alternatives to fill the gap for those patients who do not have matched related donor or unrelated donor and the outcome of these types of transplantations are expected to be better than chemotherapy alone or even better than autologous stem cell transplant for selected indications. All of these advances result in steadily increasing numbers of long-term survivors after allo-HSCT, creating an expanding pool of children, and young and mature adults who are at risk of long-term complications of allo-HSCT.

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Problems Among Long-Term Survivors 

For long-term survivors (>2 years post-HSCT), the prospect for long-term survival is excellent (85% at 10 years after HSCT). Yet, among long-term survivors, mortality rates are four- to ninefold higher than observed in an age-adjusted general population for at least 30 years after HSCT, yielding an estimated 30% lower life expectancy compared with someone who has not been transplanted.13, 14 The most common causes of excess deaths other than recurrent malignancy are chronic GVHD, infections, second malignancies, respiratory diseases, and cardiovascular disease and many other late effects.13, 14, 15, 16, 17

Chronic GVHD is a multisystem chronic alloimmune and autoimmune disorder that occurs later after allo-HSCT. It is characterized by immunosuppression, immune dysregulation, decreased organ function, significant morbidity, and impaired survival. Approximately 10% to 30% of patients require continued immunosuppressive treatment beyond 5 years from the initial diagnosis of chronic GVHD.18, 19 Therefore, it is not surprising that corticosteroid and other immunosuppressive therapies are major contributors of late complications after allo-HSCT. If not treated adequately and in severe cases, chronic GVHD can result in major disability related to keratoconjunctivitis sicca, pulmonary insufficiency due to bronchiolitis obliterans, or restrictive lung disease related to scleroderma or fasciitis, as well as joint contractures, skin ulcers, esophageal and vaginal stenosis, and many other long-term complications.2, 3, 5

Several factors impact on recovery from and late effects of allo-HSCT, including prior therapy for the underlying disease, pretransplant comorbidities and psychosocial status, intensity of the transplant conditioning regimen, and most importantly duration of chronic GVHD and immunosuppressive therapy.3, 20, 21, 22, 23

Other complications are related to the prolonged use of glucocorticoids and other immunosuppressive drugs, and many (eg, cardiovascular events, chronic pulmonary disease, endocrine complications, and secondary malignancies) are multifactorial in etiology. Side effects of the treatment of acute complications early after HSCT (eg, the use of corticosteroids) may also contribute to long-term complications. Nearly all organ systems can be affected by late effects of allo-HSCT.

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Perspective 

Ongoing research is focused on better understanding of late effect issues and prediction of post-transplant long-term complications, which allows transplant eligible patients to incorporate this knowledge into more informative decision making. Therefore, significant resources should be focused on the better implementation of how patients and physicians use extensive data regarding post-transplant late complications in clinical care.

With survivorship, a shift in care occurs from large transplant centers to community healthcare providers. As a result, many hematologist/oncologist and primary care physicians are assuming the post-HSCT late effects care of long-term survivors. Preventive measures as well as early detection and treatments are important aspects to reducing morbidity and mortality in long-term survivors after allo-HSCT. Therefore, this issue of Seminars offers practical advice and outlines late effect experts personal approaches in managing long-term survivors after allo-HSCT.

We also recommend early referral or discussion with a transplant center for enrollment of patients in available late effect studies and for management guidelines. A better understanding of the pathogenesis of late effects will allow for more effective screening to identify patients at risk prior to the allo-HSCT procedure, and allow more effective monitoring to detect early evolution of the late effects after allo-HSCT. This may, in turn, allow for improved therapeutic decision making while evaluating patients for HSCT, and early institution of treatments directed at preventing and treating late effects in patients at risk after allo-HSCT

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References 

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 Declaration of commercial interest: none

PII: S0037-1963(11)00108-9

doi:10.1053/j.seminhematol.2011.10.014

Seminars in Hematology
Volume 49, Issue 1 , Pages 1-3, January 2012

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