|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
From the University of Minnesota, Minneapolis, MN; Fred
Hutchinson Cancer Research Center, Seattle, WA; Dana-Farber Cancer
Institute, Boston, MA; Memorial Sloan-Kettering Cancer Center, New
York, NY; City of Hope National Medical Center, Duarte, CA; and the
National Marrow Donor Program, Minneapolis, MN.
Allogeneic bone marrow transplantation (BMT) offers the
only curative therapy for chronic myelogenous leukemia. We compared prospectively collected results of 2464 unrelated donor (URD) transplantations with 450 HLA-identical, matched sibling donor (MSD)
transplantations performed at collaborating National Marrow Donor
Program institutions. A total of 63% of URDs were matched at HLA-A,
-B, and at -DRB1 alleles; all MSDs were genotypically identical at
major histocompatibility loci. URD recipients were younger (median 36 vs 39, P = .001) than MSDs and underwent BMT later after
diagnosis (median 17 [0-325 months] vs 7 [1-118 months], P = .001) and less often in chronic phase (CP) (67% vs
82%, P = .001). Multivariate analysis demonstrated a
significantly increased risk of graft failure and acute graft versus
host disease after URD BMT. The risk of hematologic relapse was low
after either matched URD or MSD transplantations. We observed
significantly though modestly poorer survival and disease-free survival
(DFS) after URD transplantations. However, for those undergoing
transplantation during CP within 1 year from diagnosis, 5-year DFS was
similar or only slightly inferior after matched URD versus MSD
transplantation (age < 30: URD 61% ± 8% vs MSD 68% ± 15%,
P = .18; 30-40: URD 57% ± 9% vs MSD 67% ± 10%,
P = .05; > 40: URD 46% ± 9% vs MSD 57% ± 9%,
P = .02). Delay from diagnosis to BMT in CP patients led
to substantially poorer 5-year DFS after matched URD than MSD BMT (CP
1-2 years: URD 39% ± 6% vs MSD 63% ± 12%; beyond 2 years: URD
33% ± 7% vs MSD 50% ± 20%). Outcome of matched URD BMT for
early CP chronic myelogenous leukemia yields survival and DFS
approaching that of MSD transplantation. However, delay may compromise
URD outcomes to a greater extent. Improvements in URD and MSD
transplantation are still needed, and results of newer,
nontransplantation therapies should be evaluated against the
established curative potential of URD and MSD marrow transplantation.
(Blood. 2002;99:1971-1977) Allogeneic bone marrow transplantation (BMT) is
currently the only curative therapy for chronic myelogenous leukemia
(CML).1-6 Both the pretransplantation chemoradiotherapy
conditioning and the allogeneic immune antitumor effect are responsible
for leukemic cell eradication and extended leukemia-free
survival.7-10 While matched sibling donor (MSD) and
unrelated donor (URD) allografts have been well recognized as suitable
and potentially curative therapeutic opportunities, the distinctive
clinical course, complications, and outcomes of these 2 allograft
approaches have not been directly compared.11-16 We
prospectively collected data on MSD transplantations performed at
institutions participating with the National Marrow Donor Program
(NMDP) to compare the results of MSD and URD BMT for CML. We herein
report detailed results of this comparative analysis, including
assessment of engraftment, graft versus host (GVH) disease, relapse,
and leukemia-free survival.
Patients included in this analysis were those with CML who
received bone marrow transplantation from MSD (n = 450) and URD (n = 2464) with data reported to and collected by the NMDP
using prospectively designed data capture methods, auditing,
centralized compilation, and data error correction at the
NMDP.16,17
Patients and characteristics
Unrelated marrow donors were identified through the NMDP, and marrow
was collected following established procedures through NMDP-approved
donor and collection centers. Transplantations were performed at 127 NMDP-affiliated transplantation centers. Specifications for donor
search and identification, marrow collection and transportation, and
data gathering and analysis were performed according to procedures developed by the NMDP as described.16,17
Unrelated donor/recipient HLA molecular typing for
DRB118,19 was performed prior to transplantation or
retrospectively using pretransplantation samples that had been
cryopreserved. Serologic testing for HLA-A and -B as well as molecular
testing for -DRB1 identified donor/recipient mismatching at A or B in 402 cases (16%). These included mismatch at HLA-A (n = 225) or HLA-B
(n = 172) or both (n = 1); data on 4 were missing. These 402 were
analyzed as partially matched. The remaining 2062 URD transplants
matched at HLA-A and -B were also DRB1-matched at the allele level in
1559 cases (63% of URD transplants).18,19 Allele typing
for class I loci was not available for this analysis. Sibling donor
transplants were serologically matched at the HLA-A, -B and -DR
regions in all 450 cases.
Pretransplantion conditioning included fractionated or single-dose
total body irradiation along with cyclophosphamide, either alone or in
combination with other chemotherapeutic agents in 2340 cases (287 MSD
and 2053 URD transplantations). Only 574 patients received
chemotherapy-only conditioning (without radiation), most often busulfan
plus cyclophosphamide. In vivo GVH disease prophylaxis using
cyclosporine or tacrolimus along with methotrexate or prednisone was
used in 2271 patients (373 MSD and 1898 URD), while 555 received ex
vivo T-cell-depleted marrow. T-cell depletion was more frequently employed for URD transplantation (P = .02).
Statistical analysis
Patient outcome was analyzed to the date of last reported follow-up or the date of death. Engraftment (neutrophil recovery to 0.5 × 109/L [500/µL]) required survival to day +22, and patients without engraftment were considered graft failures.20 Death before day +22 (100 URD, 8 MSD) and incomplete data (14 URD) excluded patients from analyses of engraftment. Relapse was analyzed as hematologic relapse. Cytogenetic sampling or reverse transcriptase-polymerase chain reaction analyses of the BCR-ABL molecular abnormality was not routinely performed at defined, scheduled posttransplantation intervals, resulting in potential reporting bias as well as imprecision in the assessment of the clinical outcome following such observations. Survival was calculated by the method of Kaplan and Meier.21 In the calculation of time-to-event for analysis of relapse, engraftment, or GVH disease where early death could alter the assessment frequency, the cumulative incidence method was used.22 In univariate analyses, the log-rank test statistic was employed to compare differences in outcome among subgroups, and the 95% confidence intervals were calculated from the SEs. In multiple regression analyses for engraftment, acute and chronic GVH disease, hematologic relapse, survival, and disease-free survival (DFS), the logistic regression (engraftment) or proportional hazards model23 was employed including the following covariates: donor and recipient age, gender, cytomegalovirus (CMV) serology, disease stage, interval from diagnosis to transplantation, donor/recipient HLA matching [class I matched or mismatched; DRB1 matched or mismatched; or number of loci mismatched HLA-A, -B, -DRB1 (0-3)], total body irradiation containing conditioning (yes/no), T-lymphocyte depletion (yes/no), and year of transplantation. The impact of transplantation center was assessed by a fixed effects variable. Statistical interactions of donor type (MSD or URD) with several risk factors were examined, testing if the effect of donor type varies among subgroups of patients identified by these risk factors. No such interactions were detected. The data collection period for MSD BMT (1991-1995) differed from the extended period of URD data collection (1988-1999). For the 233 URD transplantations that preceded and 1396 URD transplantations that followed the MSD cohort, we analyzed the era of URD BMT as an added variable in Cox regression models but observed no effect of URD transplantations that preceded (P = .41) or followed (P = .32) the 1991 to 1995 MSD era on DFS following BMT (not shown).
Timing of BMT As shown in Table 1, BMT using MSD occurred sooner after diagnosis than URD (median 7 vs 17 months, P = .001). This may be attributable to delays in decision making and donor availability that complicate URD transplantation. The average time for donor searching until transplantation was shorter for transplantations performed in first chronic phase (CP1) versus those in accelerated phase or after blast phase (mean search time 322, 419, and 418 days, respectively, P = .004). Even in the CP transplantations, search time was shorter to identify matched URD donors (mean 267 days) than partially matched URD (mean 377 days, P = .0001) though there was no statistically significant interaction between disease stage at transplantation and HLA match (P = .14).Engraftment Posttransplantation recovery to neutrophil level 0.5 × 109/L (500/µL) was quicker and more likely after MSD versus URD transplantation. As shown in Table 2, significantly more patients undergoing URD matched or partially matched transplantations failed to achieve engraftment. Additionally, transplantations for CML beyond CP1 were associated with a lower likelihood of successful engraftment. As shown in Figure 1, for CP1 patients, graft failure occurred by day +100 in 1% ± 1% (95% confidence limits) of MSD, 4% ± 1% of matched URD, and 8% ± 2% of partially matched URD transplantations (P < .0001).
Acute and chronic GVH disease Advanced acute GVH disease (grade III-IV) occurred significantly more frequently after URD transplantation. As shown in Table 2, for BMT during CP, compared with MSD transplantations, matched URD transplantations were 1.31 times more likely (P = .01) to result in acute GVH disease and partially matched URD had a 1.83 times greater likelihood of acute GVH disease (P = .0001). Transplantations beyond CP1 (especially in blast phase) were associated with more frequent acute GVH disease. In addition, GVH disease was significantly more frequent in transplantations from older donors and in transplantations performed beyond 1 year from diagnosis. Interferon therapy prior to BMT was associated with a lower risk of acute GVH disease. As shown in Figure 2, in CP patients the 100-day cumulative incidence of grade III-IV GVH disease was only 26% ± 5% in MSD, 35% ± 3% in URD matched, and 49% ± 5% in URD partially matched transplantations (P < .0001).
Chronic GVH disease occurred more frequently after URD transplantation
as well. Table 2 shows that there was a nearly 1.5-fold greater risk of
chronic GVH disease after URD transplantation when compared with MSD
BMT. This increased risk was similar following matched and partially
matched URD BMT. In addition, chronic GVH disease was more frequent in
transplantations performed beyond the CP and using a female donor.
Figure 3 shows the cumulative incidence
of chronic GVH disease in patients undergoing transplantation in CP1.
As shown, at 2 years 53% ± 5% of MSD recipients, 60% ± 3% of
URD matched recipients, and 60% ± 6% of URD partially matched recipients developed chronic GVH disease (P = .07).
Hematologic relapse Hematologic relapse was uncommon and occurred with similar frequency in recipients of MSD (n = 42, 9.3%) or URD (n = 199, 8.1%) transplants (P = .39). As shown (Table 2), the donor type had only modest impact on hematologic relapse after transplantation. However, relapse was significantly more frequent in transplantations beyond the CP1, in older patients, and in patients receiving marrow from a male donor. Hematologic relapse was infrequent when performed in CP1: 5% to 8% for all 3 donor types (Figure 4A) (P = .24). As shown in Figure 4B, while the risk of relapse was higher for those undergoing transplantation beyond the CP (17%-20%), it was still similar after MSD or URD transplantation (P = .54).
Donor lymphocyte infusions Donor lymphocyte infusions (DLIs) were given to only 68 (2.8%) patients after URD BMT. DLIs were given to 32 URD patients following CML relapse; of the 32, 17 had received a T-depleted graft. Two received DLIs for prevention of hematologic relapse (1 had received T-depleted BM). Fourteen others, 12 with T-depleted BM, received DLIs for management of B-cell lymphoproliferative disease, 4 for graft failure, 3 for management of viral infection, and 13 for unspecified reasons. DLIs were given to 17 (3.8%) MSD recipients, 16 for treatment of relapse (3 recipients of T-depleted marrow). Thus, of 555 recipients of T-depleted BM, 52 received DLI treatments compared with 33 DLIs in 2359 recipients of unmanipulated grafts (P = .001).Survival and DFS Patients in this series had a median follow-up of 2.1 years (range 0-11) in the URD recipients and 4.8 years (range 0.3-6.1) in the MSD recipients, although 233 (24%) of URD survivors have been followed for more than 5 years after BMT. A total of 988 (40.1%) URD and 268 (59.6%) MSD recipients are alive. Multivariate analysis showed better survival after MSD versus URD transplantations and significantly better survival for transplantations performed in CP (Table 3). Superior survival was seen in younger patients, in CMV-seronegative recipients, following transplantation (in CP) within 1 year of diagnosis, and in transplantations using younger donors. Even for transplantations performed during CP1, 5-year survival was superior for MSD (63% ± 5%) compared with matched URD (45% ± 3%) or partially matched URD (31% ± 5%) transplantation (Figure 5A, P = .0001). These differences were still apparent, with substantially poorer 5-year survival for transplantations performed beyond CP1 (Figure 5B, MSD 31% ± 11%; matched URD 20% ± 4%; partially matched URD 16% ± 6%, P = .002).
Prolonged survival without leukemia relapse is, of course, the desired
outcome following allogeneic transplantation. As shown in Table 3, DFS
was best after MSD versus URD transplantation, best when performed in
CP, and significantly better for younger patients (and a trend with
younger donors), for CMV-seronegative recipients and, importantly, for
patients undergoing transplantation within 1 year of diagnosis. These
prognostic indicators (donor type, disease phase, recipient age, and
time from diagnosis to transplantation) had a major impact on both
individual cohort outcome and on the comparison between URD and MSD
BMT. As shown in Figure 6, for patients
undergoing transplantation within 1 year of diagnosis, still within the
CP1, patients aged less than 30 years, 30 to 40 years, and more than 40 years have superior 5-year DFS with MSD versus matched URD BMT, though
the differences are modest (age < 30: MSD 68% ± 15% vs matched
URD 61% ± 8%, P = .18; 30-40: MSD 67% ± 10% vs
matched URD 57% ± 9%, P = .05; > 40: MSD
57% ± 9% vs matched URD 46% ± 9%, P = .02).
As shown in Figure 7, 5-year DFS for
patients in CP is best with a less than 1-year interval from diagnosis
to BMT. Delay until BMT had a greater adverse impact on URD
transplantation. There is little decrement in DFS for MSD recipients
undergoing transplantation more than 1 year from diagnosis when
compared with those undergoing transplantation within the first year
(P = .41). However, while DFS after matched URD BMT is
similar to MSD in the early (< 1 year) CP patients, DFS in the
URD cohort is substantially worse after a delay of more than 1 year from diagnosis (Figure 7B, P = .0001). Similar
falloff in DFS with longer diagnosis to BMT interval is observed with
partially matched URD as well (Figure 7C, P = .02).
Therefore, the outcome for transplantation in CP within 1 year from
diagnosis is comparable in matched URD and MSD recipients, but for BMT
delayed beyond 1 and 2 years the outcome for the URD recipients is
notably worse.
While only 20 years ago no curative therapy existed for CML, now
allotransplantation can cure a sizable fraction of
patients.1-6,11-16 Other advances have shown that
In this report, we show the comparative value of MSD and URD allografts for treatment of CML in the largest cohort of allotransplantation recipients to be studied. Although the outcome overall is superior in the MSD cohort, certain populations of patients have remarkably similar outcomes after matched URD and MSD transplantations. Patients in CP receiving transplants within 1 year from diagnosis enjoy more than 60% DFS after MSD transplantations and 55% DFS at 5 years following matched URD transplantation. Both delay beyond 1 year and delay until clinical acceleration of the leukemia markedly compromises outcome, especially for URD recipients. Therefore, the clinical choice of transplantation versus other therapies in the early CP becomes even more vexing for those lacking an available related donor. Delay from diagnosis until MSD or URD transplantation has been previously reported to compromise clinical outcome.1-3,14-16 Although subclinical disease acceleration (even without basophilia, fibrosis, rising blast percentage, or cytogenetic evolution) may contribute to the poorer results accompanying later transplantations, other mechanisms may be operative. These may include immune compromise due to replacement of normal dendritic cells or natural killer cells with BCR-Abl-positive effectors. Inconsistent findings have been reported regarding the adverse effect of prolonged (> 6 or 12 months) interferon therapy preceding allogeneic URD transplantation. Few earlier reports have contrasted the outcomes of MSD versus URD transplantations for leukemia, primarily in children.29-31 Similar, though more complex, clinical courses followed the URD allografts. The immediate or early hazards of graft failure, infection, GVH disease, and death would certainly give pause to all patients facing the choice of pharmacologic versus transplantation therapy soon after diagnosis. However, formal decision analyses (prepared before the era of tyrosine kinase inhibitors) that have weighed these results support the choice of early transplantation for patients with an available donor. However, the post-BMT survival advantage is not seen until 4 or more years following transplantation.32 Even with the encouraging results reported herein, this survival advantage might not be realized until even later following URD transplantation. Recent reports suggest that outcomes after URD BMT may be further improved by allele matching of class I and II histocompatibility between donors and recipients.33,34 Despite these data, however, treatment guidelines have weighed heavily against early transplantation in favor of hoped-for improvements in medical therapy without loss of curative potential of early allotransplantation.35,36 In view of the current results showing quite good outcomes for younger, early CP transplantations using either MSD or matched URD donors and the substantive survival penalty for delay, the strategies of deferred BMT may be questioned. Our results strongly document the importance of early URD transplantation. We recognize need for improvements in survival following URD transplantation, especially when performed beyond CP and beyond the first year after diagnosis. For the most favorable group, however, including early CP patients up to age 40, new nontransplantation approaches must be tested as rigorously in prospective fashion to best help patients and their physicians make the optimal clinical choice.
Submitted July 19, 2001; accepted November 5, 2001.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Daniel J. Weisdorf, University of Minnesota
1. Thomas ED, Clift RA, Fefer A, et al. Marrow transplantation for the treatment of chronic myelogenous leukemia. Ann Intern Med. 1986;104:155-163. 2. Goldman JM, Apperley JF, Jones L, et al. Bone marrow transplantation for patients with chronic myeloid leukemia. N Engl J Med. 1986;314:202-207[Abstract].
3.
Goldman JM, Szydlo R, Horowitz MM, et al.
Choice of pretransplant treatment and timing of transplants for chronic myelogenous leukemia in chronic phase.
Blood.
1993;82:2235-2238
4.
Clift RA, Buckner CD, Thomas ED, et al.
Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide.
Blood.
1994;84:2036-2043
5.
Gale RP, Hehlmann R, Zhang M-J, et al.
Survival with bone marrow transplantation versus hydroxyurea or interferon for chronic myelogenous leukemia.
Blood.
1998;91:1810-1819 6. van Rhee F, Szydio RM, Hermans J, et al. Long term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 1997;20:553-560[CrossRef][Medline] [Order article via Infotrieve]. 7. Apperley JF, Mauro FR, Goldman JM, et al. Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: importance of a graft-versus-leukemia effect. Br J Haematol. 1988;69:239-245[Medline] [Order article via Infotrieve]. 8. Devergie A, Reiffers J, Vermant JP, et al. Long-term follow-up after bone marrow transplantation for chronic myelogenous leukemia: factors associated with relapse. Bone Marrow Transplant. 1990;5:379-386[Medline] [Order article via Infotrieve].
9.
Kolb HJ, Mittermueller J, Clemm C, et al.
Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients.
Blood.
1990;76:2462-2465 10. Collins RH Jr, Rogers ZR, Bennet M, Kumar V, Nikein A, Fay JW. Hematologic relapse of chronic myelogenous leukemia following allogeneic bone marrow transplantation: apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppression. Bone Marrow Transplant. 1992;10:391-395[Medline] [Order article via Infotrieve].
11.
McGlave PB, Beatty P, Ash R, Hows JM.
Therapy for chronic myelogenous leukemia with unrelated donor bone marrow transplantation: results in 102 cases.
Blood.
1990;75:1728-1732
12.
Drobyski WR, Ash RC, Casper JT, et al.
Effect of T-cell depletion as graft-versus-host disease prophylaxis on engraftment, relapse, and disease-free survival in unrelated marrow transplantation for chronic myelogenous leukemia.
Blood.
1994;83:1980-1987
13.
Spencer A, Szydlo RM, Brookes PA, et al.
Bone marrow transplantation for chronic myeloid leukemia with volunteer unrelated donors using ex vivo or in vivo T-cell depletion: major prognostic impact of HLA class I identity between donor and recipient.
Blood.
1995;86:3590-3597 14. Devergie A, Apperley JF, Labopin M, et al. European results of matched unrelated donor bone marrow transplantation for chronic myeloid leukemia. Impact of HLA class II matching. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 1997;20:11-19[CrossRef][Medline] [Order article via Infotrieve].
15.
Hansen JA, Gooley TA, Martin PJ, et al.
Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia.
N Engl J Med.
1998;338:962-968
16.
McGlave PB, Shu XO, Wen W, et al.
Unrelated donor marrow transplantation for chronic myelogenous leukemia: nine years' experience of the National Marrow Donor Program.
Blood.
2000;95:2219-2225 17. Standards of the National Marrow Donor Program. NMDP Standards Committee. Transfusion. 1993;33:172-180[CrossRef][Medline] [Order article via Infotrieve].
18.
Petersdorf EW, Longton GM, Anasetti C, et al.
The significance of HLA-DRB1 matching on clinical outcome after HLA-A, B, DR identical unrelated donor marrow transplantation.
Blood.
1995;86:1606-1613 19. Petersdorf EW, Hurley C, Dupont B, et al. Analysis of 328 marrow transplants for the treatment of chronic myeloid leukemia from unrelated donors facilitated by the US National Marrow Donor Program (NMDP): effect of HLA-DRB1 allele disparity on clinical outcome [abstract]. Blood. 1996;88(suppl):268a.
20.
Davies SM, Kollman C, Anasetti C, et al.
Engraftment and survival after unrelated donor bone marrow transplantation: a report from the National Marrow Donor Program (NMDP).
Blood.
2000;96:4096-4102 21. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457-481[CrossRef]. 22. Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representation of old estimators. Stat Med. 1999;18:695-706[CrossRef][Medline] [Order article via Infotrieve]. 23. Cox DR. Regression models and life tables. J Royal Stat Soc. 1972;34:187-220.
24.
Kantarjian HM, Smith TL, O'Brien S, Beran M, Pierce S, Talpaz M.
Prolonged survival in chronic myelogenous leukemia after cytogenetic response to interferon-
25.
Guilhot F, Chastang C, Michallet M, et al.
Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group.
N Engl J Med.
1997;337:223-229
26.
Interferon alfa versus chemotherapy for chronic myeloid leukemia: a meta-analysis of seven randomized trials: Chronic Myeloid Leukemia Trialists' Collaborative Group.
J Natl Cancer Inst.
1997;89:1616-1620
27.
Druker BJ, Talpaz M, Resta D, et al.
Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.
N Engl J Med.
2001;344:1031-1037
28.
Druker BJ, Sawyers CL, Kantarjian H, et al.
Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome.
N Engl J Med.
2001;344:1038-1042 29. Locatelli F, Pession A, Comoli, et al. Role of allogeneic bone marrow transplantation from an HLA-identical sibling or a matched unrelated donor in treatment of children with juvenile chronic myeloid leukemia. Br J Haematol. 1996;92:49-54[CrossRef][Medline] [Order article via Infotrieve]. 30. Hongeng S, Krance R, Bowman L, et al. Outcomes of transplantation with matched sibling and unrelated donor marrow in children with leukemia. Lancet. 1997;350:767-771[CrossRef][Medline] [Order article via Infotrieve]. 31. Gustafsson A, Remberger M, Winiarski J, Ringdén O. Unrelated bone marrow transplantation in children: outcome and a comparison with sibling donor grafting. Bone Marrow Transplant. 2000;25:1059-1065[CrossRef][Medline] [Order article via Infotrieve].
32.
Lee SJ, Kuntz KM, Horowitz MM, et al.
Unrelated donor bone marrow transplantation for chronic myeloid leukemia: a decision analysis.
Ann Intern Med.
1997;127:1080-1088
33.
Sasazuki T, Juji T, Morishima Y, et al.
Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow Donor Program.
N Engl J Med.
1998;339:1177-1185
34.
Petersdorf EW, Gooley TA, Anasetti C, et al.
Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient.
Blood.
1998;92:3515-3520 35. Gratwohl A, Hermans J, Goldman JM, et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet. 1998;352:1087-1092[CrossRef][Medline] [Order article via Infotrieve].
36.
Silver RT, Woolf SH, Hehlmann R, et al.
An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: developed for the American Society of Hematology.
Blood.
1999;94:1517-1536
© 2002 by The American Society of Hematology.
| ||||||||||
 |
|
 |
|
  J. Schetelig, M. Bornhauser, C. Schmid, B. Hertenstein, R. Schwerdtfeger, H. Martin, M. Stelljes, U. Hegenbart, K. Schafer-Eckart, M. Fussel, et al. Matched Unrelated or Matched Sibling Donors Result in Comparable Survival After Allogeneic Stem-Cell Transplantation in Elderly Patients With Acute Myeloid Leukemia: A Report From the Cooperative German Transplant Study Group J. Clin. Oncol., November 10, 2008; 26(32): 5183 - 5191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. S. Fox, F. A. Chervenak, and L. B. McCullough Ethical Considerations in Umbilical Cord Blood Banking Obstet. Gynecol., January 1, 2008; 111(1): 178 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cutler, S. Li, V. T. Ho, J. Koreth, E. Alyea, R. J. Soiffer, and J. H. Antin Extended follow-up of methotrexate-free immunosuppression using sirolimus and tacrolimus in related and unrelated donor peripheral blood stem cell transplantation Blood, April 1, 2007; 109(7): 3108 - 3114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Yakoub-Agha, F. Mesnil, M. Kuentz, J. M. Boiron, N. Ifrah, N. Milpied, S. Chehata, H. Esperou, J.-P. Vernant, M. Michallet, et al. Allogeneic Marrow Stem-Cell Transplantation From Human Leukocyte Antigen-Identical Siblings Versus Human Leukocyte Antigen-Allelic-Matched Unrelated Donors (10/10) in Patients With Standard-Risk Hematologic Malignancy: A Prospective Study From the French Society of Bone Marrow Transplantation and Cell Therapy J. Clin. Oncol., December&nb |
Top
Abstract
Introduction
-interferon, with or without cytarabine, can extend time in CP and
prolong survival.
Mayo
Mail Code 480, 420 Delaware St SE, Minneapolis, MN 55455; e-mail: