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Patient-reported outcomes after unrelated donor transplant better with bone marrow than peripheral blood
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Patients who underwent hematopoietic stem cell transplantation with bone marrow from unrelated donors reported better 5-year outcomes than those who received peripheral blood, according to long-term follow-up data from a randomized trial.
Bone marrow recipients reported improved psychological well-being and less troublesome graft-versus-host disease (GVHD) symptoms. They also appeared more likely to return to work.
Stephanie J. Lee
More transplants are performed from unrelated donors than related donors, according statistics from the Center for International Blood and Marrow Transplant Research. More than 80% of transplants from unrelated donors use peripheral blood rather than bone marrow.
Results from a large randomized trial published in 2012 showed that both graft sources produced similar survival, nonrelapse mortality and relapse rates. Transplant recipients who received bone marrow had higher rates of graft failure (P = .002), whereas those who received peripheral blood had higher rates of chronic GVHD (P = .01).
Stephanie J. Lee, MD, MPH, PhD, professor of medicine at University of Washington School of Medicine and member of the Fred Hutchinson Cancer Research Center, and colleagues conducted a long-term analysis of patient-reported outcomes from this trial.
Study participants had diagnoses of acute or chronic leukemia, myelodysplasia or myelofibrosis.
The researchers collected preliminary data at the time of enrollment, with follow-up data collected 6 months, 1 year, 2 years and 5 years after transplantation.
Patients completed several validated self-assessments. These included the Functional Assessment of Cancer Therapy–Bone Marrow Transplant, which measures physical, social, emotional and functional domains; the Mental Health Inventory, which measures psychological well-being, psychological distress, anxiety, depression, positive affect, and loss of behavior and personal control; and the Lee Chronic GVHD symptom scale, which measures symptoms in the skin, lungs, eyes and mouth, as well as energy, nutrition and overall psychological status.
Additionally, the researchers collected data on self-assessed performance status, overall health and quality of life.
The investigators collected occupational data through questions about job status, type of work, number of hours of paid and unpaid labor, school attendance, work importance, and changes to work goals.
A total of 195 study participants (bone marrow, n = 102; peripheral blood, n = 93) remained alive 5 years after transplantation. More than half of the participants (53.5%; n = 104) were aged 40 years or older, and men comprised 51.8% (n = 101) of the cohort.
Approximately 70% of study participants completed baseline assessments. At baseline, patients assigned to HSCT with bone marrow reported higher functional well-being (P = .01), total Functional Assessment of Cancer Therapy scores (P = .02) and Health Rating Scale scores (P = .03).
Response rates at predetermined assessment time points during the first 2 years after transplant ranged from 28% to 43%.
Participants in the bone marrow group had higher chronic GVHD skin scores at 6 months (P = .009), whereas participants in the peripheral blood group had higher chronic GVHD mouth scores at 2 years (P = .03). No other differences occurred during the first 2 years.
Factors associated with missing outcomes data at 5 years included younger age and high-risk disease; however, graft source was not associated with missing data (OR = 1.05; 95% CI, 0.52-2.14).
The patient-reported outcome response rate for each instrument ranged between 74% and 78% at the 5-year interval.
Overall mean scores favored the bone marrow group for the Functional Assessment of Cancer Therapy survey (mean and standard deviation, 76.7 [1.6] vs. 70.5 [1.9]; P = .01), the Mental Health Inventory Psychological Well-Being survey (78.9 [1.7] vs. 72.2 [1.9]; P = .01) and Lee Chronic GVHD symptoms scores (13.1 [1.5] vs. 19.3 [1.6]; P = .004).
Seventy-one percent (n = 72) of responding survivors in the bone marrow group had no chronic GVHD at 5 years, compared with 49% (n = 46) of the peripheral blood group. Bone marrow recipients also had lower rates of mild GVHD (17% vs. 23%), moderate GVHD (9% vs. 17%) and severe GVHD (4% vs. 9%; P = .03).
Participants in the bone marrow group had a higher 5-year likelihood of returning to full- or part-time work (OR = 1.5; 95% CI, 1.2-2). Fifty-two percent (n = 42) of 5-year survivors in the bone marrow group reported returning to work, compared with 40% (n = 29) of the peripheral blood group.
Undergoing transplantation with matched unrelated bone marrow correlated with better functional well-being (P = .02), higher health rating scale scores (P = .02) and perceptions of overall quality of life (P = .04).
This cohort also had better GVHD symptom scores in the eyes (P < .001) and lungs (P = .004), as well as higher energy scores (P = .003).
Both cohorts had similar rates of OS (bone marrow vs. peripheral blood, 40% vs. 39%), relapse (32% vs. 29%) and treatment-related mortality (29% vs. 32%).
The researchers acknowledged study limitations, including the overall lack of data from approximately 25% of study participants, as well as the low response rates at 6 months, 1 year and 2 years.
“The failure to see an increase in the proportion of [HSCTs] using bone marrow means that the clinical results published were not compelling enough to change treatment of these patients,” Lee and colleagues wrote. “It remains to be seen whether the additional information provided by this study will be judged sufficient to recommend bone marrow instead of peripheral blood for unrelated donor transplantation when performed for the indications and using the approaches included in this study.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Edward A. Copelan
Early studies of bone marrow transplantation demonstrated that higher doses of bone marrow cells led to more rapid and more reliable engraftment, with less infectious mortality. The ability to procure much higher doses of hematopoietic progenitors from blood compared with marrow triggered a transition from the use of marrow to peripheral blood for allogeneic hematopoietic cell transplant.
Peripheral blood donation allowed donors to avoid bone marrow harvest under anesthesia and its threefold higher incidence of serious adverse events. Evidence of decreased relapse rates and better survival in patients with high-risk disease who received peripheral blood compared with marrow transplants from human leukocyte antigen (HLA)–identical siblings further increased enthusiasm for the use of peripheral blood, including in unrelated recipients, for whom approximately 80% of transplants now utilize peripheral blood. The only reported disadvantage to the use of peripheral blood in place of marrow in HLA–identical sibling transplants is increased incidence of acute and chronic graft-versus-host disease (GVHD).
Clinicians have inferred that the favorable results from HLA–identical transplants would apply to unrelated transplants, despite the greater genetic disparity and higher incidence of GVHD in unrelated transplantation. The previous finding from this randomized study demonstrating similar outcomes but a higher incidence of chronic GVHD in unrelated transplants receiving peripheral blood compared with marrow should have been concerning to clinicians; however, the use of peripheral blood did not decrease following that report.
This long-term follow up of that study is even more concerning, clearly demonstrating the significant adverse effect of receiving peripheral blood on quality of life 5 years after transplant. These results remind clinicians of the value of prospective randomized studies that are specific for the situation in question and the danger of applying results from one group of patients to another. Knowing what we know now, the shift to peripheral blood instead of marrow in patients undergoing unrelated HCT — based on minimal data — may not have been wise.
Ironically, however, just as the studies on HLA–identical sibling transplants should not be applied to unrelated transplants, the relevance of this study to patients undergoing unrelated transplantation today is less than clear. The extent of genetic disparity — responsible for a greater incidence of chronic GVHD — tolerated in this study is substantially greater than generally occurs today. Only intermediate resolution typing for HLA A and HLA B was required, and 5/6 matches were permitted. In addition, only a limited number of GVHD prevention regimens were permitted. High-dose posttransplant cyclophosphamide, which lowers the incidence of chronic GVHD and is increasingly being utilized, was not permitted.
Despite these limitations, this study clearly identifies the long-term downside of substituting peripheral blood for marrow and merits consideration by clinicians.
Disclosure: Copelan reports no relevant financial disclosures.
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