Page 1103 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 61 Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome in Adults 973

No. of patients
Donor No-donor Favors Favors
Source group group No. of trials HR (95% Cl) donor group no-donor group
1
Shiller et al, 1992 28 54 1.91 (0.95-3.84)
2
Archimbaud et al, 1994 27 31 1.04 (0.52-2.11)
Hewlett et al, 1995 53 110 0.98 (0.65-1.49)
3
Sierra et al, 1996 47 68 1.60 (0.96-2.65)
4
5
Keating et al, 1998 295 377 0.88 (0.72-1.09)
6
Slovak et al, 2000 89 174 0.82 (0.57-1.18)
7
Suciu et al, 2003 293 441 0.85 (0.67-1.08)
8
Jourdan et al, 2005 182 290 0.81 (0.63-1.05)
Burnett et al, 2006 428 877 0.87 (0.74-1.03)
9
10
Cornelissan et al, 2007 326 599 0.89 (0.74-1.08)
Overall survival benefit (fixed effects) 1768 3021 15 0.90 (0.82-0.97)
Sensitivity analyses for overall survival
benefit for AML in first remission
Random effects meta-analysis 1768 3021 15 0.90 (0.82-1.00)
Adjusted HR 1768 3021 15 0.89 (0.81-0.97)
Including cytogenetic risk-stratified trials 2057 3549 21 0.87 (0.80-0.94)
(fixed effects)
Including cytogenetic risk-stratified trials 2057 3549 21 0.87 (0.78-0.98)
(random effects)
Including cytogenetic risk-stratified trials 2057 3549 21 0.86 (0.79-0.93)
(adjusted HR)
Overall survival benefit by cytogenetic risk
Good-risk AML 188 359 10 1.07 (0.83-1.38)
Intermediate-risk AML 864 1635 14 0.83 (0.74-0.93)
Poor-risk AML 226 366 14 0.73 (0.59-0.90)
2
Test for heterogeneity: χ = 5.29; P = .07;
2
2
J = 62.2%
0.1 1.0 10
Death, HR (95% Cl)
Fig. 61.1 META-ANALYSIS OF OVERALL SURVIVAL BENEFIT IN FIRST COMPLETE REMISSION
OF ACUTE MYELOID LEUKEMIA FOR YOUNGER ADULTS. AML, Acute myeloid leukemia;
CI, confidence interval; HR, hazard ratio. (Redrawn from Koreth J, Schlenk R, Kopecky KJ, et al: Allogeneic stem cell
transplantation for acute myeloid leukemia in first complete remission: Systematic review and meta-analysis of prospective
clinical trials, JAMA 301:2349, 2009. Sources cited within Fig. 61.1 can be found following the reference list online at
expertconsult.com.)

impaired survival, RIC and MAC regimens had similar overall and Unrelated Adult Donors
leukemia-free survival. Although a small randomized trial documented
25
similar outcomes of MAC versus RIC transplantation in AML-CR1, Given the very poor outcomes after nonallogeneic therapy in poor-
a larger prospective randomized trial of MAC versus RIC transplanta- risk AML, and the documented benefit of HLA-matched sibling
tion in AML or MDS patients (Blood and Marrow Transplantation donor HSCT, clinical practice has been to undertake HLA-matched
Clinical Trials Network protocol 0901) closed after accrual of 272 of unrelated donor transplantation for younger adults with poor-risk
planned 356 patients because of an increased relapse risk in the RIC AML in CR1 who lack sibling donors. A retrospective analysis of
arm (http://www.nlm.nih.gov/databases/alerts/2014_nhlbi_bmt_ HLA-matched sibling compared with unrelated donor HSCT in
ctn.html). RIC transplantation does, however, offer the option of poor-risk AML-CR1 documented comparable outcomes with HLA-
curative allogeneic HSCT in older or sicker patients with AML-CR matched siblings and HLA well-matched unrelated donors with
26
for whom the toxicity of MAC transplantation might be prejudicial. 3-year OS of 45% compared with 53% (p = .63). Outcomes were
Conversely, patients with good performance status but high AML not as good for partially HLA-mismatched unrelated donors (one-
relapse risk might be preferentially selected for MAC. locus HLA mismatch), with 3-year OS of 31% (p = .026). Smaller
prospective studies have also shown equivalent results, confirming the
suitability of well-matched unrelated donor HSCT in poor-risk
Alternative Donor Transplantation AML. 27,28
There is limited data comparing HLA-matched sibling with
HSCT from an HLA-matched sibling donor has been the standard unrelated donors in intermediate-risk AML, although at least one
29
of care for prospective biologic treatment assignment studies evaluat- study documented similar outcomes with either donor type. Current
ing postremission therapies. Patients lacking sibling donors could be practice is to offer HLA-matched unrelated donor HSCT to
considered for alternative donors: unrelated adult donors, UCB, or intermediate-risk AML patients in first remission, especially if there
haploidentical donor transplantation. are adverse molecular lesions.