Marrow Donor Program (NMDP) as of October 1, 1991, and more than 850 .... nurse or medical technologist, surveyed donors by telephone 1 or 2 days following their ..... Community Blood Bank, St Petersburg, FL; Florida Reference Labs,.
From bloodjournal.hematologylibrary.org by guest on July 15, 2011. For personal use only.
1993 81: 1940-1946
Experiences of the first 493 unrelated marrow donors in the National Marrow Donor Program DF Stroncek, PV Holland, G Bartch, T Bixby, RG Simmons, JH Antin, KC Anderson, RC Ash, BJ Bolwell and JA Hansen
Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub_requests Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints Information about subscriptions and ASH membership may be found online at: http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml
Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. Copyright 2011 by The American Society of Hematology; all rights reserved.
From bloodjournal.hematologylibrary.org by guest on July 15, 2011. For personal use only.
Experiences of the First 493 Unrelated Marrow Donors in the National Marrow Donor Program By David F. Stroncek, Paul V. Holland, Glenn Bartch, Todd Bixby, Roberta G. Simmons, Joseph H. Antin, Kenneth C. Anderson, Robert C. Ash, Brian J. Bolwell, John A. Hansen, Joanna M. Heal, P. Jean Henslee-Downey, Ernst R. Jaffe', Harvey G. Klein, Peter M. Lau, Herbert A. Perkins, Mark A. Popovsky, Thomas H. Price, Scott D. Rowley, Linda C. Stehling, Paul L. Weiden, Mary E. Wissel, and Jeffrey McCullough More than 410,000 people participated in the National Marrow Donor Program (NMDP) as of October 1, 1991, and more than 850 volunteers had donated marrow. While the incidence of serious morbidity as a result of bone marrow donation is rare, the incidence of lesser complications and the long-term consequences of marrow donation are not known. To determine the incidence of donor complications and measure the recovery time of volunteer, unrelated marrow donors, we analyzed the results of surveys of the first 493 persons who donated marrow through the NMDP. The marrows were collected at 42 centers. The median age of the donors was 37.9 years (range 19.1 to 55.6 years). The median volume of marrow collected was 1,050 mL (range 180 to 2,983 mL). Autologous red blood cells were transfused to 89.8% (439) of donors but only 0.6% (3) of donors received allogeneic blood. Acute complications related to the collection procedure occurred in 5.9%of donors; but a serious complication, apnea during anesthesia, occurred in only one donor. When donors were questioned approximately 2 days following discharge from their hospitalization, most donors described symptoms related to the collection; 74.8%experiencedtiredness, 67.8% experienced pain at the marrow collection site, and 51.6%
of the donors experienced low back pain. Donors were surveyed repeatedly until they felt that they had recovered completely. Mean recovery time was 15.8 days; however, 42 (10%)donors felt that it took them 230 days to recover fully. The duration of the marrow collection procedure and duration of anesthesia both positively correlated with donor pain and/or fatigue following the collection; but the duration of the collection procedure had the highest correlation with post-collection pain and fatigue. The volume of marrow collected per unit of donor weight was more weakly correlated with donor pain and/or fatigue than the anesthesia and collection times. When multivariate analysis was used to analyze the correlation between donor recovery time and these variables, only the duration of the collection was found to correlate significantly with donor recovery time (P = .001).This analysis demonstrates that marrow donation is well tolerated with few complications. To decrease further the incidence of donor discomfort and recovery time following donation, the duration of the collection procedure, and probably the duration of anesthesia, and the volume of marrow collected, should be kept to a minimum. 0 1993 by The American Society of Hematology.
B
blood centers established files of HLA-typed, potential marrow donors. After these blood centers demonstrated that HLA-typed apheresis donors could be recruited into marrow donor registries and that people would donate marrow for a stranger,'-'' the National Marrow Donor Program (NMDP) was established in 1986." Through the efforts ofthe NMDP, the number of transplants performed with marrow from unrelated donors has increased dramatically. As of October 1, 199 1, more than 4 10,000potential marrow donors were registered with the NMDP and more than 850 transplants with marrow from these unrelated donors had been facilitated. While several studies have found that the marrow donation procedure rarely results in death or life-threatening complications to the marrow d ~ n o r , ' ~ little . ' ~ ~is' ~ known of the incidence of minor complications, long-term consequences, and the time necessary for donors to recover. However, to obtain informed consent from potential marrow donors, accurate data are necessary for describing the incidence and nature of minor as well as serious donor complications, plus the time necessary for donors to recover fully from the marrow donation procedure. It is important to identify and avoid aspects of the donation process that might adversely affect marrow donors so attempts can be made to improve the safety and comfort of the donation process. This is especially true for individuals who donate marrow for strangers. In this study we reviewed the results of marrow collections and post-collection donor surveys for all donations by unrelated marrow donors facilitated by the NMDP over a 35-month period.
EFORE THE MID 1980s, almost all allogeneic marrow transplants performed used marrow from HLA identical siblings. Following reports that marrow transplants using marrow from unrelated donors could be used successfullyto treat patients with severe combined immune deficiency, chronic myelogenous leukemia, and acute leukemia,'.' several
From the UniversityofMinnesota; SacramentoMedical Foundation Blood Center; University of Pittsburgh; Brigham and Women's Hospital; Dana-Farber Cancer Institute; Medical College of Wisconsin; Cleveland Clinic Foundation; Fred Hutchinson Cancer Research Center: American Red Cross Rochester Regional Blood Services; University of Kentucky; Albert Einstein College of Medicine: NIH Clinical Center; Irwin Memorial Blood Bank; American Red Cross Northwest Ohio Blood Centers; Puget Sound Blood Center; Blood Systems Inc; American Red Cross Central Ohio Regional Blood Services; Virginia Mason Clinic; and the American Red Cross St Paul Regional Blood Services. Submitted May I , 1992; December I , 1992. Supported in part by Contracts No. NOOO14-86-C-0575from the US Navy Medical Research Institute and No. NOI-HB-97075 from the National Heart, Lung and Blood Institute. Address reprint requests to David F. Stroncek, MD. Department of LaboratoryMedicine di Pathology,Box 198 UMHC, The University of Minnesota Hospital & Clinic, 420 Delaware St SE, Minneapolis, MN 55455. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with I 8 U.S.C. section I734 solely to indicate this fact. 0 1993 by The American Society of Hematology. 0006-4971/93/8107-0007$3.00/0 1940
MATERIALS AND METHODS
Marrow donors. Results of all marrow collections from unrelated donors coordinated by the NMDP between December 1, 1987 and Blood, Vol 81, No 7 (April I), 1993:pp 1940-1946
From bloodjournal.hematologylibrary.org by guest on July 15, 2011. For personal use only. EXPERIENCES OF UNRELATED MARROW DONORS November 3, 1990 were analyzed. During this period 493 people donated marrow. Three of these donors donated twice, but only experiences after the first donations were surveyed. The median age of donors was 37.9 years (range 19.1 to 55.6 years); at the time of collection, 36.5% of donors were 45 years. Overall, 46.7% of donors were women. Donors were enrolled in 53 different NMDP donor centers; eleven donor centers provided more than ten donors each and three donor centers provided more than 50 donors each. Marrow collection. After informed consent, donors underwent marrow aspiration from iliac crests using sterile technique.14Marrow was harvested at an NMDP approved marrow collection center convenient to the donor and when necessary, transported by courier to the marrow transplant hospital. The duration of anesthesia was defined as the interval between the time of induction of anesthesia and the time of discharge from the operating room. The collection time was defined as the interval between the time at the start of marrow collection and the time at the end of the marrow collection. The amount of marrow collected was determined by the differencebetween the final volume of marrow and media and the media added to the marrow, two measured items. Data collection. Marrow collection center personnel completed a standard form describing the marrow collection procedure. The amount of data collected and the format of some of the items changed as the program evolved. During the first 2 years of the program, attempts were made to collect data on new or changed items for previously reported collections. The information required for the new items was not always available. In particular, the amount of media added to the marrow frequently was not present in the hospital chart. When the final volume of media plus marrow was known but the volume of media was missing, the fraction of the final volume of media and marrow that was media was estimated for each collection facility using a regression line through the origin that was based on collections in which both measurements were available. The median fraction was 0.14, with 76% of the collection facilitieshaving fractions between 0.09 and 0.16 (the actual range was 0.08 to 0.26). The marrow donors were surveyed within 3 days following the donation. Donors were told in advance that they would be surveyed following the marrow donation. Donor center personnel, usually a nurse or medical technologist, surveyed donors by telephone 1 or 2 days following their discharge from the hospital. During this survey, donor center personnel asked standardized questions conceming donor symptoms and completed standardized forms. Among the 493 collections, forms were obtained on 482 or 97.8% of the collections. Beginning November 1988, donors were also surveyed by donor center personnel by telephone I week after the marrow was collected and weekly thereafter to assessthe donor's recovery (432 collections). Donors were asked specifically if they felt they had recovered physically and emotionally and ifthey had resumed all their normal physical and work activities. After donors reported that they had recovered completely emotionally and physically and had resumed all their previous physical and work activities, they were no longer called. Results of the telephone surveys were recorded on hard copy forms. In some cases, interviewers recorded the reasons the donors did not feel that they had completely recovered. The date of complete recovery was taken as the midpoint between the day of the survey on which the donor reported complete recovery and date of the last previous survey. Of the 432 collections with planned weekly follow-up, 430 or 99.5% were completed. Among the 482 donors at US donor centers, standardized forms were mailed to them to assess the marrow collection experience I week and I year following the marrow collection. Four hundred thirtysix or 90.5% of the donors returned the 1 week posttransplant questionnaire and 74.5% of the donors returned the 1 year form. These
1941
questions were part of a questionnaire sent to donors to measure the psychosocial effects of the marrow d0nati0ns.l~ Statistical analysis. Statistical analysis was performed using Pearson correlation coefficients, logistic regression, and multivariate linear regression. RESULTS
Marrow collection. Marrow was collected at 42 different collection centers. The median number of marrows collected by each center was 7 with a range of 1 to 68. General anesthesia was used in 77.8% of collections, spinal in 7.5%, and epidural in 14.6%.Data were not available for one collection. The median duration of anesthesia was 1 I O minutes (range 30 to 355 minutes), and the median time to collect the marrow was 60 minutes (range 8 to 196 minutes) (Table l). The median volume of marrow collected was 1,050 mL (range 180 to 2,983 mL) and the median volume of marrow collected per unit weight of donor was 13.6 mL/kg (range 2.1 to 39.3 mL/kg) (Table 1). The total volume of marrow collected correlated directly with the duration of the collection procedure ( r = .2; P = .0001) and the duration of anesthesia (r = .2; P =
.0001).
Almost all donors were transfused with red blood cells (RBCs) during the collection procedure. Overall, 89.8% (data
Table 1. Duration of Anesthesia, Duration of Collection, and Volume of Marrow Aspirated from Unrelated Marrow Donors No. of Donors
Duration of anesthesia (min) t120 120-180
>180 Total Data not available Duration of collection (min) t60 60-90
>90 Total Data not available Volume collected (mL) 1,750 Total Data not available Volume collected per unit of donor mass (mL/kg) 110
10-1 2.4 12.5-14.9 15.0-17.4 17.5-19.9 >20 Total Data not available
Percent
250 152
56.2 34.2
43
9 . 7
445 48
100.0
185 135
45.7 33.3
85
21.0
405 88
100.1
84 86 135 77 30
19.8 20.3 31.8 18.2 7.1
12
2.8
424 69
100.0
103 71 80 71 42
24.4 16.8 19.0 16.8 10.0
55
13.0
422 71
100.0
From bloodjournal.hematologylibrary.org by guest on July 15, 2011. For personal use only. 1942
STRONCEK ET AL
Table 2 . Donor Experiences 48 to 7 2 Hours Following the Marrow Collection
Table 3. Problems Noted by Donors 7 to 14 Days After Marrow Collection
Experience
Missing
Total
Percent of Donors Reporting Each Experience
Tiredness Pain at donation site Low back pain Pain with sitting Pain with walking Trouble climbing stairs Nausea Vomiting Prolonged bleeding at site of donation
12 12 12 12 13 27 12 12
48 1 48 1 48 1 48 1 480 466 48 1 48 1
74.8 67.8 51.6 49.7 62.5 41.2 55.3 36.6
12
48 1
9.4
A Lot N'
Fatigue Pain at donation site Low back pain Difficulty walking Problems sleeping Nausea or vomiting Light headedness Fainting Bleeding Infection Pain at IV site
433 433 433 433 433 433 433 433 433 433 433
(%I 24.0 27.3 23.3 13.9 6.0 4.8 4.6 0.5 0.9 0.0 9.0
A Little (%)
Not At All (%)
56.1 60.3 50.3 52.9 28.9 16.9 28.2 2.8 17.8 3.5 39.3
18.5 11.3 24.9 31.6 63.5 76.9 65.8 95.2 79.2 94.7 50.1
Total Missing
(%I 1.4 1.2 1.4 1.6 1.6 1.4 1.4 1.6 2.1 1.8 1.6
Number of donors completing the questionnaire.
missing for four) of donors were transfused with 2 1 U of autologous blood. A single unit of autologous blood was transfused to 131 (26.8%) donors, 2 U were transfused to 25 1 ( 5 I .3%)donors, and 2 3 U were transfused to 57 ( 1 1.7%) donors. Three donors were transfused with allogeneic blood two were transfused with 2 U, and one with 1 U. One donor each received 2 U of autologous whole blood, 2 U of autologous plasma, and 500 mL of 5% albumin. No donors were transfused with allogeneic platelets or fresh frozen plasma. The length of time donors remained hospitalized vaned greatly among collection centers. Some centers admitted patients to the hospital the day of collection while other centers admitted patients to the hospital the night before the procedure. Only 14.8%of donors spent < 18 hours in the hospital, while 41.1% spent 18 to 36 hours hospitalized, and 44.2% spent >36 hours in the hospital. Because the length of stay following the donation varied for each collection facility as a result of different policies, the duration of the hospital stay was not used when investigating factors related to donor discomfort and/or complications. Donor complications. As a result of the marrow collection procedure, 29 (5.9%) donors experienced an acute complication. Six donors suffered from problems related to hypotension; two of these donors had an episode of syncope. Four donors had febrile episodes requiring an extension of their hospital stay and/or treatment with antibiotics. The hospital stay was extended for four other donors due to pain at the site where marrow was aspirated. Post-dural puncture headaches occurred in three of the patients who received spinal or epidural anesthesia. Phlebitis at the site of a peripheral intravenous catheter occurred in three donors. Prolonged nausea delayed the discharge of two donors and skin rash related to medications occurred in two donors. One donor each experienced numbness of the tongue; bleeding at the collection site, requiring the donor to be seen by the collection physician; erythema at the collection site, requiring treatment with antibiotics; and a single episode of hematuria following the collection. In addition, one donor experienced an apneic episode during the administration of spinal anesthesia. This complication resolved completely and the marrow was collected successfully.
Donors were surveyed several times following the marrow collection. Donor center nurses interviewed the donor by telephone 48 to 72 hours after the marrow collection procedure and the results are shown in Table 2. Not unexpectedly, most donors experienced some pain or fatigue. Donors were also surveyed by mail 7 to 14 days following the marrow collection. Again, the results of this survey indicate that most donors experienced some pain, fatigue, or difficulty walking following the marrow collection procedure (Table 3). However, when the donors were asked if they had suffered a side effect or complication related to donating marrow, only 28.9% said yes. Donors were surveyed by telephone weekly following the collection until each donor reported complete emotional and physical recovery. While most donors had recovered from the procedure within 19 days of the donation procedure, 54 of 430 (12.6%)donors indicated that they had not recovered completely by 30 days (Table 4). However, in 1 I cases the donors were contacted within 12 days of the collection, but were not contacted again until 30 days following the collection or were not contacted at all until 30 days following the collection. Thus, the time of recovery could not be determined accurately for these donors. Of the 419 donors who were
Table 4. Frequency Distribution of Days to Complete Recovery Determined by Weekly Telephone Surveys Days to Recovery'
No. of Donors
Percent
