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Chapter 106 Haploidentical Hematopoietic Cell Transplantation 1629

HLA-Haploidentical Versus HLA-Matched URD SCT GVHD (36% vs. 13%; p < .001), grades III–IV acute GVHD (10%
vs. 3%; p = .004), and chronic GVHD (42% vs. 15%; p < .001)
than patients receiving grafts from matched siblings. However, there
GIAC Protocol were no significant differences between recipients of haplo versus
matched sibling transplants in the 3-year incidence of relapse (15%
The Beijing group and the European Society for Blood and Marrow vs. 15%; p = .98) or NRM (13% vs. 8%; p = .13) or for 3-year DFS
Transplantation conducted a retrospective comparison of patients with (74% vs. 78%; p = .34) or 3-year OS (79% vs. 82%; p = .36).
AML and intermediate-risk cytogenetics receiving haploidentical
transplants using the GIAC protocol (n = 87) versus control subjects
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receiving fully matched (10/10) URD transplants (n = 87). Cases Posttransplant Cyclophosphamide
and control subjects were matched for age ±5 years, interval from CR1
to transplant, and the number of induction courses required to achieve A variety of reports from single centers have retrospectively analyzed
CR1. Outcomes were similar in both groups: The 5-year LFS was the outcomes of transplants from either matched siblings or haploi-
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60.3% in the URD group versus 73.5% in the haplo group (p = .15), dentical first-degree relatives. 183–186 Bashey et al reported that
OS was 63.6% versus 78.2% (p = .15), relapse incidence was 24% patients treated with haploBMT plus PTCy experienced a higher
versus 12.7% (p = .08), and NRM was 15.7% versus 13.8% (p = .96). incidence of acute GVHD (41% vs. 21%; p = .005) and significantly
worse survival (58% vs. 72%; p = .02). The other studies did not
show significantly worse survival after haploidentical BMT, and
Posttransplant Cyclophosphamide two 185,186 showed a significantly lower incidence of chronic GVHD
without a corresponding increase in relapse.
The CIBMTR has compared outcomes of URD BMT with those of The CIBMTR recently compared outcomes of patients with
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haploBMT plus PTCy for patients with AML as well as for patients lymphoma undergoing RIC followed by either HLA-matched sibling
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with lymphoma. For patients with AML, neutrophil recovery by day SCT (n = 807) or HLA-haploidentical BMT with PTCy as part of
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30 was lower after haploidentical compared with matched unrelated GVHD prophylaxis (n = 180). Although platelet recovery was
donor (MUD) transplants (90% vs. 97%; p = .02), but 3-month acute delayed among those treated with haploBMT plus PTCy, the cumu-
GVHD grades II–IV (16 vs. 33%; p < .0001) and 3-year chronic lative incidence of chronic GVHD was significantly lower after
GVHD (30% vs. 53%; p < .0001) incidence favored the haploidentical haploBMT (12% vs. 45%; p < .001), and there were no significant
group. Similar differences in GVHD were also seen after nonmyeloab- differences between haploBMT and HLA-matched sibling BMT in
lative conditioning. Three-year probability of OS after myeloablative 3-year rates of NRM (15% vs. 13%; p = .41), relapse/progression
conditioning was 45% after haplo transplants versus 50% after MUD (37% vs. 40%; p = .51), PFS (48% vs. 48%; p = .96), or OS (61%
transplants (p = .38). Corresponding rates after RIC were 46% for vs. 62%; p = .82).
haplo and 44% for MUD transplants (p = .71)
The study of patients with lymphoma was restricted to those
receiving RIC only and compared three groups: haploidentical PRACTICAL CONSIDERATIONS IN HLA-HAPLOIDENTICAL
transplants with PTCy versus URD transplants, with or without STEM CELL TRANSPLANT
ATG. The 1-year cumulative incidence rates of chronic GVHD were
13%, 51%, and 33% among patients receiving haploBMT with The following sections provide management recommendations for
PTCy, URD BMT without ATG, and URD BMT with ATG, clinical situations that are frequently encountered and for which
respectively (p < .001). In multivariate analysis, grades III–IV acute the donor relationship and immunologic disparity require unique
GVHD was higher in URD without ATG (p = .001), as well as URD consideration.
with ATG (p = .01), relative to haploidentical transplants. Cumula-
tive incidence rates of relapse/progression at 3 years were 36%, 28%,
and 36% in the haploidentical, URD without ATG, and URD with Selection of the HLA-Haploidentical Donor (see
ATG groups, respectively (p = .07). Corresponding 3-year OS rates Box 106.2)
were 60%, 62%, and 50%, respectively, in the three groups, with
multivariate analysis showing no survival difference between URD Potential HLA-haploidentical donors include parents, children, sib-
without ATG (p = .21) or URD with ATG (p = .16) relative to lings, half-siblings, cousins, nieces, nephews, and grandchildren. In
haploidentical transplants. The data demonstrate that, for patients our experience, each patient has, on average, two or three potential
with lymphoma, haploidentical transplants with PTCy produce HLA-haploidentical first-degree relatives who are willing and medi-
survival outcomes as good as those seen after transplants using URDs, cally able to donate. Several patient and donor characteristics influ-
but with less chronic GVHD. ence the choice of donor, including medical and psychologic
suitability of the donor, donor age, sex, and parity, presence of
antidonor HLA antibodies in the patient’s serum, donor-recipient
HLA-Haploidentical Versus HLA-Matched HLA mismatch, red blood cell ABO group compatibility, and donor
Sibling Donors and recipient CMV serology. Regardless of transplant platform, there
are two absolute contraindications to donation: (1) the donor is
medically or psychologically unfit to donate, or (2) the recipient has
GIAC Protocol antibodies against donor HLA molecules at a level that would produce
a positive result in a CDC assay (see Management of the Patient with
Single-center, nonrandomized studies suggested that survival after Antidonor HLA Antibodies section later).
HLA-haploidentical SCT using the GIAC protocol or after HLA- The transplant platform used may also influence donor choice. In
matched sibling SCT was similar. 106,181 These studies motivated a a study of 118 patients receiving megadose T cell–depleted trans-
prospective, multicenter trial in which patients with AML in CR1 plants, 5-year event-free survival was better in patients who received
were assigned to receive a transplant after myeloablative conditioning transplants from the mother than from the father (50.6% ± 7.6% vs.
from an HLA-matched sibling (n = 219) or, if a matched sibling was 11.1% ± 4.2%; p < .001), with better survival resulting from both a
not available, an HLA-haploidentical donor (n = 231) with treatment reduced incidence of relapse and transplant-related mortality. The
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to the GIAC protocol. Patients assigned to the haplo arm were 5-year event-free survival was 27.0% ± 6% and 25.5% ± 9% for
significantly younger (median age, 28 years) than patients receiving patients who received transplants from an HLA haploidentical sister
matched sibling grafts (median age, 40 years). Patients receiving (n = 30) or brother (n = 49), respectively (p = .63). On the basis of
haplo grafts had significantly higher incidence of grades II–IV acute these results, the authors suggested that the mother of the patient