Biology of Blood and Marrow Transplantation
Volume 14, Issue 9, Supplement , Pages 8-15, September 2008

Twenty Years of Unrelated Donor Hematopoietic Cell Transplantation for Adult Recipients Facilitated by the National Marrow Donor Program

  • Chatchada Karanes

      Affiliations

    • City of Hope National Medical Center, Duarte, California
    • ,
  • Gene O. Nelson

      Affiliations

    • National Marrow Donor Program, Minneapolis, Minnesota
    • ,
  • Pintip Chitphakdithai

      Affiliations

    • National Marrow Donor Program, Minneapolis, Minnesota
    • ,
  • Edward Agura

      Affiliations

    • Baylor University Medical Center, Dallas, Texas
    • ,
  • Karen K. Ballen

      Affiliations

    • Massachusetts General Hospital, Boston, Massachusetts
    • ,
  • Charles D. Bolan

      Affiliations

    • Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • David L. Porter

      Affiliations

    • University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
    • ,
  • Joseph P. Uberti

      Affiliations

    • Karmanos Cancer Institute, Detroit, Michigan
    • ,
  • Roberta J. King

      Affiliations

    • National Marrow Donor Program, Minneapolis, Minnesota
    • ,
  • Dennis L. Confer

      Affiliations

    • National Marrow Donor Program, Minneapolis, Minnesota
    • Corresponding Author InformationCorrespondence and reprint requests: Dennis L. Confer, MD, National Marrow Donor Program, 3001 Broadway Street NE, Suite 100, Minneapolis, MN 55413.

Received 5 June 2008; accepted 5 June 2008.

Article Outline

Abstract 

For more than 20 years the National Marrow Donor Program has facilitated unrelated donor hematopoietic cell transplants for adult recipients. In this time period, the volunteer donor pool has expanded to nearly 12 million adult donors worldwide, improvements have occurred in the understanding and technology of HLA matching, there have been many changes in clinical practice and supportive care, and the more common graft source has shifted from bone marrow (BM) to peripheral blood stem cells (PBSCs). The percentage of older patients who are receiving unrelated donor transplants is increasing; currently over 1 in 10 adult transplant recipients is over the age of 60 years. Chronic myelogenous leukemia (CML) was previously the most common diagnosis for unrelated donor transplantation, but it now comprises less than 10% of transplants for adult recipients. Transplants for acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and myelodysplastic syndromes (MDS) all outnumber CML. Treatment-related mortality (TRM) has declined significantly over the years, particularly in association with myeloablative transplant preparative regimens. Correspondingly, survival within each disease category has improved. Particularly gratifying are the results in severe aplastic anemia (AA) where 2-year survival has doubled in just 10 years.

Key Words: National Marrow Donor Program, NMDP, Adult, Hematopoietic, Stem Cell, Transplantation

 

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Introduction 

Since its establishment in 1987, >30,000 unrelated donor hematopoietic cell transplants (HCT) have been facilitated by the National Marrow Donor Program (NMDP). HCT recipients in >70% of cases were adults with hematologic malignancies or acquired hematologic conditions. The history of the NMDP has been recently reviewed [1]. Much has changed in 20 years, including a vastly increased volunteer adult donor pool, introduction of peripheral blood stem cells (PBSCs), addition of umbilical cord blood (UCB) units, and dramatic advances in HLA-typing and matching technology. Additional advances include the introduction of new pharmaceutical agents, refinement of conditioning regimens through strategies such as targeted dosing and reduced-intensity conditioning (RIC), and the application of post-transplant immunomodulation. This review will examine the experiences of adult recipients of HCT facilitated by the NMDP over the past 20 years.

Data Collection 

The study population included 11,418 adult patients 18 years or older who received unrelated donor (URD) transplants through the NMDP from December 1987 through March 2006 for acute myelogeneous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogeneous leukemia (CML), myelodysplastic disorders (MDS), non-Hodgkin lymphoma (NHL), Hodgkin disease (HD), multiple myeloma (MM), and severe aplastic anemia (SAA). Only AML, ALL, CML, MDS, and SAA recipients with a primary unrelated donor transplant and NHL, HD, and MM recipients with a primary URD transplant or a URD second transplant with a prior autologous transplant were included in the study population. Data from this cohort were collected on standard NMDP forms and included predominately U.S. recipients, and only those from whom informed consent was documented. A total of 1488 recipients were omitted from the study because of consent issues.

These data were grouped into 4 time periods (1987-1995, 1996-1998, 1999-2002, and 2003-2006) of similar length and approximately similar numbers of patients. A longer early period (1987-1995) was chosen to have enough cases for analysis.

Statistical Analysis and Definitions 

Probabilities of survival were calculated using the Kaplan-Meier method. Survival curves were truncated at 2 years because of short follow-up in the most recent time period. With second transplants for NHL, the first 2 time periods were collapsed because of small sample sizes. Neutrophil engraftment was defined as an achievement of an absolute neutrophil count of ≥500 neutrophils/mm3 sustained for 3 consecutive laboratory measurements on different days. Platelet engraftment was defined as an achievement of a platelet count recovery of ≥50,000 platelets/mm3 sustained for 3 consecutive laboratory measurements on different days with no platelet transfusions in the previous 7 days. Probabilities of neutrophil and platelet engraftment were calculated using the cumulative incidence method, with death without engraftment as a competing risk. Treatment-related mortality (TRM) was defined as death without relapse, and was calculated using the cumulative incidence method, with relapse treated as a competing risk. Engraftment and TRM were censored at occurrence of a second transplant. Chi-square tests were used for pointwise rate comparisons.

Disease risk was defined as early (first complete remission for acute leukemia, first chronic phase for CML, and MDS-refractory anemia or acquired idiopathic sideroblastic anemia), intermediate (first relapse or second or greater complete remission for acute leukemia, and second chronic phase or accelerated phase for CML), or advanced (second or greater relapse for acute leukemia, CML-blast phase, and MDS-refractory anemia with excess blasts, or refractory anemia with excess blasts in transformation). Disease risk was not classified for NHL, HD, myeloma, or SAA. Myeloablative conditioning regimens included 1 of the following: total body irradiation (TBI) dose >500 cGy as a single fraction, TBI dose >800 cGy regardless of the number of fractions, melphalan (Mel) dose >150 mg/m2, busulfan (Bu) dose ≥9.5 mg/kg, any combination of Mel and Bu, or any combination of Cyclophosphamide (Cy), Etoposide (VP-16), and TBI. All other regimens were considered non-myeloablative/reduced intensity conditioning (RIC). Based on the best available typing data at the time of analysis, HLA matching was classified into 3 categories (well-matched, partially matched, and mismatched) according to a recently developed algorithm that considers level of HLA-typing resolution and matching at HLA-A, -B, -C, and -DRB1 loci [2]. Well-matched cases had either no identified HLA mismatch and informative data at 4 loci or allele matching at HLA-A, -B, and -DRB1. Partially matched pairs had a defined, single locus mismatch and/or missing HLA data. Mismatched cases had ≥2 allele or antigen mismatches.

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Results 

Numbers and characteristics of adult HCT patients in the study population during each of the 4 time periods are shown in Table 1. Fifty-six percent of patients with AML, ALL, CML, or MDS were transplanted with intermediate or advanced disease during the most recent period, compared to 53% from 1987 through 1998. Over time, the use of HCT in older age patients has increased. The median age of adult patients has increased by 11 years to 46.7 years, with 11% of patients in the most recent period (2003-2006) aged >60 years. Patients receiving well-matched donors accounted for 65% for all HCTs during 2003-2006, compared to 28% of patients transplanted during 1987-1995 and 1996-1998.

Table 1. Characteristics of Adult Recipients December 1987-March 2006
1987-19951996-19981999-20022003-2006
N%N%N%N%
Number of recipients2052 1930 3224 4212
Follow-up time among survivors in Days
Median (range)4536(273-7034)3296(371-4293)2154(120-3247)757(63-1739)
Diagnosis
Acute myelogenous leukemia (AML)422214692496730163939
Acute lymphoblastic leukemia (ALL)22711241125021652813
Chronic myelogeneous leukemia (CML)106552802426832140510
Myelodysplastic disorders (MDS)1769213114391459414
Non-Hodgkin lymphoma (NHL)53311264011260914
Hodgkin lymphoma (HD)7<11218732045
Multiple myeloma (MM)2414128331193
Severe aplastic anemia7844026221143
Disease Risk AML, ALL, CML, MDS
Early841447624495637112436
Intermediate674365653388934111535
Advanced33118338205722266921
Unknown status or unclassified44260317472588
Time from diagnosis to transplant in months
Median (range)16.2(0-325)13.3(0-309)12.5(0-316)12.9(0-316)
<61829288156151998823
6-12550275913193929102624
12-2461930533287602488821
≥24689345082688627128931
Unknown12110124121<1
Recipient age in years
Median (range)35.6(18.0-58.8)38.6(18.0-65.9)41.5(18.0-79.3)46.7(18.0-78.1)
18-3510615280142116636121629
36-6099148112258192860252460
61-70007<1126445311
≥7100004<119<1
Graft type
Bone marrow20521001930100223769118028
PBSC000096930291369
Cord blood unit00001811193
HLA match
Well matched5752854528165951274565
Partially matched6423188946104833108526
Mismatched8354149626517163679
Unknown00000015<1
Conditioning regimen
Myeloablative177286182294236673229454
Reduced intensity/nonmyeloablative593105585627191145
Unknown221113<12<17<1
First transplant NHL, HD, myeloma
Yes6881123753005340744
No; prior autologous161942252714752556

HD indicates Hodgkin lymphoma.

Indications for Transplants 

The distribution of diseases for which unrelated donor HCT was preformed has changed dramatically over time (Figure 1). In the most recent time period, patients in the study population with AML accounted for 39% of unrelated donor HCTs followed by NHL (14%), MDS (14%), and ALL (13%) (Table 1). CML was previously the single most common indication for unrelated donor HCT (52% of all transplants from 1987 through 1995), but only accounted for 10% of HCTs in the most recent time period. Among 4212 adults transplanted from unrelated donors from 2003 to 2006, only 5% had HD, 3% myeloma, and 3% SAA.

  • View full-size image.
  • Figure 1. 

    Number of adult transplants in the study population for each disease by transplant period. Transplant numbers for all diseases except CML have increased over the 4 time periods.

HLA Matching 

There has been an increasing percentage of HLA well-matched donor-recipient pairs over time (Table 1). In the 2 early time periods, only 28% of the donor-recipient pairs met the definition of well-matched in contrast to 51% and 65% in 1999-2002 and 2003-2006, respectively. Frequency of HLA-mismatching category has similarly declined over time (41%, 26%, 16%, and 9%, respectively).

Stem Cell Sources 

Bone marrow was the only graft source available for primary unrelated donor HCT through the NMDP until July of 1999. Since the introduction of a protocol for collection of PBSC, there has been a steady increase in the use of this graft source. In the study population during the period from 2003 to 2006, PBSC accounted for 69% of all unrelated donor HCT. There were 137 adult patients who received UCB unit transplantation through the NMDP in this analysis.

Engraftment 

Only patients receiving myeloablative preparative regimens were analyzed for neutrophil and platelet engraftment. The cumulative incidence of neutrophil engraftment was 95% for patients in the 2003-2006 period compared to 90% for the period from 1987-1995 (P < .0001). The median time to neutrophil engraftment among patients who engrafted was 19 days in 1987-1995, 18 days in 1996-1998, 17 days in 1999-2002, and 15 days in 2003-2006. Platelet engraftment to 50,000 occurred in 70% of patients transplanted in 2003-2006 compared to only 27% in 1987-1995. The median time to platelet engraftment among patients who engrafted was 33 days in 1987-1995, 32 days in 1996-1998, 28 days in 1999-2002, and 23 days in 2003-2006.

TRM 

For leukemia and MDS patients receiving bone marrow following myeloablative regimens, the TRM at 100 days, 1 year, and 2 years decreased significantly over the time intervals studied. One hundred-day TRM was 35%-36% in the periods 1988-1995 and 1996-1998 and decreased to 28% in 1999-2002 and 16% in 2003-2006 (P < .0001) (Table 2). Similar decreases in TRM were observed at 1 year and 2 years posttransplant. One hundred-day TRM for patients receiving PBSC grafts with myeloablative conditioning declined from 25% to 18% in the intervals 1999-2002 and 2003-2006, respectively (P = .005). Among these patients there was also decreasing TRM at 1 and 2 years (Table 2).

Table 2. Treatment-Related Mortality for Adult Recipients with Leukemia and Myelodysplastic Syndromes
1988-19951996-19981999-20022003-2006
NProb (%)95% CINProb (%)95% CINProb (%)95% CINProb (%)95% CIPointwise P-value
Myeloablative bone marrow1647 1666 1648 711
at 100 days post-HCT 3533-38 3633-38 2826-30 1614-19<.0001
at 1 year post-HCT 5350-55 5149-53 4139-44 2825-31<.0001
at 2 years post-HCT 5654-59 5452-57 4543-48 3229-36<.0001
Myeloablative PBSC0 0 448 1270
at 100 days post-HCT — — 2521-29 1816-20.005
at 1 year post-HCT — — 4237-47 3128-33<.0001
at 2 years post-HCT — — 4541-50 3532-38.0002
Non-myeloablative bone marrow17 44 188 198
at 100 days post-HCT 3515-59 4227-57 2015-27 1712-23.01
at 1 year post-HCT 4119-65 4934-64 3528-42 3225-38.20
at 2 years post-HCT 4119-65 4934-64 3831-45 3730-44.52
Non-myeloablative PBSC 0 271 876
at 100 days post-HCT — 1915-24 1311-15.01
at 1 year post-HCT — 3731-42 2623-29.002
at 2 years post-HCT — 4135-47 3027-33.001

CI indicates confidence interval; MDS, myelodysplastic syndromes.

For patients with NHL and HD who received myeloablative unrelated donor transplants as a first transplant, there was significant improvement in TRM from the earlier time period (1990-2002) to the most recent period (2003-2006) (100-day: 35% versus 21% [P = .002], 1-year: 48% versus 32% [P = .001], and 2-year: 51% versus 37% [P = .005]). However, for NHL and HD patients who were transplanted between 2003 and 2006 and received nonmyeloablative regimens, TRM was lower still at 10%, 20%, and 25% at 100 days, 1 year, and 2 years, respectively.

TRM for patients with NHL and HD who had prior autologous transplants was high in all time periods. With myeloablative regimens, 1-year TRM was 70% prior to 1999, 44% between 1999 and 2002, and 43% for the interval 2003-2006 (P = .05). Patients with prior autologous transplants who received non-myeloablative regimens exhibited lower TRM (∼25% at 1 year), which has not changed over time.

There has been a major reduction of TRM for SAA patients who received bone marrow transplants following non-myeloablative preparative regimens (Table 3). In the most recent time period (2003-2006) TRM at 100 days, 1 year, and 2 years was 15%, 25%, and 33%, respectively. Among 30 SAA patients who received PBSC after nonmyeloablative regimens during 2003-2006, the TRM was 20% at 100 days, 26% at 1 year, and 32% at 2 years.

Table 3. Treatment-Related Mortality for Severe Aplastic Anemia Patients Treated with Non-myeloablative Preparative Regimens
1988-19951996-19981999-20022003-2006
NProb (%)95% CINProb (%)95% CINProb (%)95% CINProb (%)95% CIPointwise P-value
Bone marrow35 26 34 54
at 100 days post-HCT 4730-64 5940-77 2411-39 157-26<.0001
at 1 year post-HCT 6245-78 6849-85 4327-60 2514-38.0001
at 2 years post-HCT 6649-81 7354-88 4327-60 3320-47.0009
PBSC0 0 8 30
at 100 days post-HCT — — 389-71 208-35.33
at 1 year post-HCT — — 6329-91 2612-43.06
at 2 years post-HCT — — 6329-91 3216-51.12

CI indicates confidence interval.

Survival Over Time for Specific Diseases 

The 2-year survival rate for AML patients has increased over time (Figure 2A). In the earlier time periods (1987-1995 and 1996-1998) survival was 21% and 20%, respectively, increasing to 31% in 1999-2002 and 37% in 2003-2006 (P < .0001). Even among patients whose donors were HLA well-matched, survival has improved over time (Figure 2B).

  • View full-size image.
  • Figure 2. 

    (A) Survival of adults with AML after HCT during 4 time periods. Survival is significantly better at 2 years post-transplant for patients transplanted during 2003-2006 compared to 1999-2002 (P ≤ .008) and also compared to 1996-1998 and 1987-1995 (P < .0001). (B) Survival of adults with AML after HLA well-matched HCT during 4 time periods. Survival is significantly better (P < .0001) at 2 years post-transplant for patients transplanted during 1999-2002 and 2003-2006 compared to patients transplanted during 1987-1998 and 1996-1998.

For ALL, the 2-year survival rate in the most recent time period was 41%, compared with values in each previous time period of 28%, 22%, and 23%, respectively (Figure 3; P < .0001). Again, similar to the observation in AML, among ALL patients with HLA well-matched donors, survival has improved over time (data not shown).

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  • Figure 3. 

    Survival of adults with ALL after HCT during 4 time periods. Survival is significantly better (P < .0001) at 2 years posttransplant for patients transplanted during 2003-2006 compared to patients transplanted during the previous periods.

The 2-year overall survival (OS) rate for patients with MDS has improved from 27%, 31%, and 32%, respectively, in the 3 early time intervals to 43% in 2003-2006 (Figure 4; P < .0001). However, when HLA match was analyzed, there has been no significant improvement of survival over time for recipients of well-matched or partially-matched grafts (data not shown). The MDS recipients of mismatched grafts from the most recent period had significantly better OS of 37% compared to 9%-19% survival when transplanted in the earlier 3 periods (P = .005).

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  • Figure 4. 

    Survival of adults with MDS after HCT during 4 time periods. Survival is significantly better (P < .0001) at 2 years post-transplant for patients transplanted during 2003-2006 compared to patients transplanted during the previous periods.

The 2-year survival rate for CML patients was 54% in 2003-2006 compared to 37% in 1987-1995 and 42% in 1996-1998 (Figure 5A; P < .0001). As shown in Figure 5B, and as expected, CML patients transplanted in first chronic phase did better than those with more advanced disease.

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  • Figure 5. 

    (A) Survival of adults with CML after HCT during 4 time periods. Survival is significantly better at 2 years post-transplant for patients transplanted during 2003-2006 compared to patients transplanted during 1987-1995 and 1996-1998 (P < .0001), but was not significantly different compared to patients transplanted during 1999-2002. (B) Survival of adults with CML in CP1, CP2/accelerated, or blast phase after HCT. Survival is significantly better (P < .0001) at 2 years post-transplant for patients transplanted during CP1 compared to the other phases. Survival is also significantly better (P < .0001) at 2 years post-transplant for patients transplanted during CP2/accelerated phase compared to blast phase.

The 2-year survival rate of patients transplanted for SAA has doubled in the past 10 years (Figure 6). Survival rates of 31% and 27%, respectively, were observed in the time periods 1987-1995 and 1996-1998. Survival in 1999-2002 jumped to 53% and climbed further to 62% in the most recent interval (P < .0001). SAA patients with HLA well-matched grafts had a 2-year survival rate of 78% in the most recent interval, 2003-2006.

  • View full-size image.
  • Figure 6. 

    Survival of adults with SAA after HCT during 4 time periods. Survival is significantly better at 2 years post-transplant for patients transplanted during 2003-2006 compared to patients transplanted during 1987-1995 and 1996-1998 (P < .0001), but was not significantly different compared to patients transplanted during 1999-2002.

Survival of NHL patients was analyzed in 2 separate categories: those who received unrelated donor HCT as first transplants and those who had prior autologous HCT. There has been significant improvement of 2-year OS over time for both groups (Table 4). In the earliest time period of 1996-1998, the 1-year and 2-year survival was 17% and 12% for patients with a prior autologous transplant compared to 1-year survival of 46% and 2-year survival of 37% in the most recent period of 2003-2006 (P = .004 at 1 year; P = .005 at 2 years). For patients who received URD HCT as a first transplant, the 1- and 2-year survival in the most recent period of 54% and 43% was better than 1- and 2-year survival of 37% and 29%, respectively, in the earlier time periods (P = .0002 at 1 year, P = .02 at 2 years).

Table 4. Overall Survival for Non-Hodgkin Lymphoma Patients—First URD Transplant and URD Transplant following a Prior Autologous Transplant
1988-19951996-19981999-20022003-2006
NProb (%)95% CINProb (%)95% CINProb (%)95% CINProb (%)95% CIPointwise P-value
First HCT51 89 263 366
at 1 year post-HCT 3725-51 3626-46 3933-45 5449-59.0002
at 2 years post-HCT 2918-43 3122-41 3328-39 4338-48.02
HCT with prior autologous0 23 136 241
at 1 year post-HCT — 175-35 4032-48 4639-52.004
at 2 years post-HCT — 122-29 3325-41 3731-43.005

CI indicates confidence interval; URD, unrelated donor.

There were only 80 patients with multiple myeloma (MM) who underwent unrelated donor HCT as a first transplant. Among 43 patients transplanted during 1987-1998, the 1-year survival was 42%, which was better than the 22% survival of 37 patients who were transplanted in the more recent interval from 1999-2006. One hundred eighty-seven myeloma patients with prior autologous transplant who subsequently underwent unrelated donor HCT had 48% 1-year survival in the period 1999-2006 compared to 20% for those transplanted from 1987-1998.

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Discussion 

These data show how practices have changed over time in the performance of URD HCT for adults. Seventy percent of adults currently receive PBSC grafts. Non-myeloablative regimens have become common and made up 45% of the transplants performed from 2003-2006. Older patients comprise an increasing percentage of the recipient population. AML is now the most common indication for URD transplantation. There has been dramatic growth in the numbers of transplants for patients with MDS, NHL, and HD. CML, which was previously the most common diagnosis for HCT, has decreased significantly since the introduction of imatinib and other tyrosine kinase inhibitors. Several factors contributed to these changes over the past 20 years. The number of volunteer donors has grown to nearly 12 million current registrants worldwide, making well-matched donors available to many more patients. More than 250,000 UCB units are also available. With this growth in available donors and UCB units, HLA diversity has also increased, enabling more patients from diverse ethnic backgrounds to access HCT therapies. Advances in the HLA typing and matching technology have facilitated more rapid identification of better-HLA-matched donors. Analyses of URD bone marrow transplants have shown the benefit of allele-level matching at HLA-A, -B, -C, and -DRB1, and potentially additional loci 3, 4, 5, 6, 7, 8, 9, 10. Several articles have also addressed best practices for optimal donor selection 11, 12, 13, 14.

There has been dramatic growth in the use of PBSC as the graft source for URD HCT. This growth was driven by transplant physicians who specify their preferred graft source once a suitable donor is identified. There should be caution with this practice as a retrospective analysis of NMDP data comparing URD HCT outcome in adults receiving PBSC and bone marrow found the rates of grade II-IV acute and chronic graft-versus-host disease (GVHD) were significantly higher in recipients of PBSC grafts [15]. There were no differences seen in TRM, leukemia recurrence, leukemia-free survival (LFS), or OS. A large randomized prospective comparison of URD bone marrow and PBSC grafts is underway, sponsored by the Blood and Marrow Transplant Clinical Trials Network, which should clarify the risks and benefits of each graft source.

Striking findings from our analysis are the decreases over time in TRM for patients in all disease categories receiving myeloablative preparative regimens. Reductions in TRM have occurred despite increasing median patient age and similar percentages of patients with intermediate and advanced disease risk. Improvements in HLA matching, better supportive care particularly in infection management, and better GVHD prophylaxis and treatment have probably played roles in the reduction of TRM [16]. TRM is low and unchanging for most transplants performed with non-myeloablative preparative regimens, except in the case of SAA for which dramatic improvements in survival and TRM have been demonstrated, particularly over the past 10 years.

Survival curves for recipients of unrelated donor grafts show clear improvements over time, with changes most evident in the recent time period from 2003 through 2006. The survival curves are unadjusted, and could reflect differences in the patient populations within each diagnosis. However, in recent years many older patients have been transplanted, more than half the patients have continued to present with intermediate or advanced disease risk at transplant, and increasingly patients come to URD transplant following a prior autologous transplant. Although better HLA matching over time clearly plays a positive role in increasing survival, improvements in survival even among the patients with well-matched donors have been demonstrated.

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Acknowledgements 

Financial Disclosure: Drs. Nelson, Chitphakdithai, King, and Confer are employees of the NMDP and have a financial relationship with the NMDP, in that capacity as employees. Drs. Karanes, Agura, Ballen, Bolan, Porter, and Uberti have nothing to disclose.

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References 

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 STATEMENT OF CONFLICT OF INTEREST: See Acknowledgements on page 15.

PII: S1083-8791(08)00249-8

doi:10.1016/j.bbmt.2008.06.006

Biology of Blood and Marrow Transplantation
Volume 14, Issue 9, Supplement , Pages 8-15, September 2008

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