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Allogeneic hematopoietic stem cell transplant (allo-HSCT) can offer a long-term cure to patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL)1. However, often human leukocyte antigen (HLA)-matched related or unrelated donors are unavailable, particularly for patients who come from ethnic minority backgrounds. In these instances, unrelated cord blood (UCB) or haploidentical (haplo) relatives may be considered donor options. Deciding between these donor options typically relies on consideration of the transplant center’s experience, donor availability, and cost. No comparative analyses between UCB and haplo donors in this setting have been conducted to date, but studies involving these donor types, with heterogenous low-intensity conditioning regimens and graft-versus-host disease (GvHD) prophylaxis, are available.
In order to compare the outcomes of patients with HL or NHL who underwent non-myeloablative haplo or UCB allo-HSCT, Giancarlo Fatobene, Vanderson Rocha, and colleagues conducted a retrospective analysis based on patient data obtained from various international stem cell transplant registries. The results of the analysis are summarized in this article and were published in the Journal of Clinical Oncology1.
Table 1. Key patient characteristics by type of donor type1
ASCT, autologous stem cell transplant; BM, bone marrow; chemo, chemotherapy; CR, complete remission; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; haplo, haploidentical; HL, Hodgkin lymphoma; MCL, mantle cell lymphoma; PB, peripheral blood; PR, partial remission; TCL, T-cell lymphoma; UCB, unrelated cord blood |
|||
|
Haplo-BM |
Haplo-PB |
UCB |
n |
357 |
169 |
214 |
Median age, years (range) |
48 (18–75) |
48 (19–75) |
48 (18–73) |
Sex, % Male Female |
37 37 |
68 32 |
64 36 |
Performance score, % 90–100 ≤80 Not reported |
74 22 4 |
62 35 3 |
69 25 6 |
Disease subtype, % HL DLBCL FL MCL TCL |
44 30 10 8 9 |
39 20 9 12 20 |
29 22 19 8 22 |
Disease status, % CR PR Chemo-refractory Untreated |
48 40 10 2 |
46 34 17 3 |
53 35 7 5 |
Prior ASCT, % |
52 |
56 |
59 |
Median follow-up, months (range) |
43 (3–100) |
30 (3–87) |
48 (3–112) |
Table 2. GvHD rates by donor type1
aGvHD, acute graft-versus-host disease; BM, bone marrow; cGvHD, chronic graft-versus-host disease; GvHD, graft-versus-host disease; haplo, haploidentical; IQR, interquartile range; PB, peripheral blood; UCB, unrelated cord blood |
|||
|
UCB |
Haplo-BM |
Haplo-PB |
Day 100 Grade 2–4 aGvHD, % (95% CI) |
43 (36–50) |
20 (16–25) |
35 (28–43) |
Day 100 Grade 3–4 aGvHD, % (95% CI) |
18 (13–24) |
5 (3–8) |
6 (3–11) |
Median time to onset of cGvHD, months (IQR) |
5 (4–8) |
6 (4–11) |
6 (4–9) |
6-month incidence of cGvHD, % (95% CI) |
17 (12–23) |
11 (8–14) |
18 (12–24) |
2-year severe cGvHD, % (95% CI) |
14 (10–20) |
8 (5–12) |
16 (10–22) |
4-year cGvHD rate, % (95% CI) |
28 (22–34) |
24 (19–29) |
32 (25–40) |
OS was significantly lower with UCB compared to haplo-BM or haplo-PB (p = 0.008), which was also true of progression-free survival (PFS, p = 0.002). Additionally, the lower survival associated with UCB transplant was attributed to higher transplant-related mortality (TRM), as shown in Table 3 and further demonstrated in multivariable analysis in Table 4.
Table 3. Efficacy outcomes by donor type1
|
UCB |
Haplo-BM |
Haplo-PB |
4-year PFS probability, % (95% CI) |
36 (30–43) |
46 (41–52) |
52 (43–61) |
4-year OS probability, % (95% CI) |
49 (42–56) |
58 (53–64) |
59 (50–68) |
4-year cumulative incidence TRM, % (95% CI) |
33 (27–40) |
20 (16–24) |
18 (13–25) |
4-year cumulative incidence of relapse/progression, % (95% CI) |
31 (25–37) |
34 (29–39) |
30 (22–38) |
BM, bone marrow; CI, confidence interval; haplo, haploidentical; PB, peripheral blood; OS, overall survival; PFS, progression-free survival; UCB, unrelated cord blood |
As shown in Table 4.
Table 4. Multivariable analysis of outcomes by donor type1
aGvHD, acute graft-versus-host disease; BM, bone marrow; cGvHD, chronic graft-versus-host disease; CMV, cytomegalovirus; haplo, haploidentical; HR, hazard ratio; OS, overall survival; PB, peripheral blood; PFS, progression-free survival; TRM, transplant-related mortality; UCB, unrelated cord blood |
||||
Outcome |
HR |
95% CI |
p value |
Adjusted for |
Grade 2–4 aGvHD UCB vs haplo-BM UCB vs haplo-PB |
1.83 1.04 |
1.37–2.44 0.76–1.43 |
< 0.0001 0.81 |
Age |
Grade 3–4 aGvHD UCB vs haplo-BM UCB vs haplo-PB |
2.61 2.31 |
1.55–4.40 1.18–4.54 |
0.0003 0.02 |
Age |
cGvHD UCB vs haplo-BM UCB vs haplo-PB |
1.53 1.01 |
1.09–2.15 0.69–1.48 |
0.02 0.97 |
— |
TRM UCB vs haplo-BM UCB vs haplo-PB |
1.91 2.27 |
1.37–2.65 1.45–3.54 |
0.0001 0.0002 |
Age, performance score, and prior ASCT |
Relapse/progression UCB vs haplo-BM UCB vs haplo-PB |
1.11 1.52 |
0.80–1.52 1.03–2.26 |
0.54 0.04 |
Age, lymphoma subtype, and disease status |
PFS UCB vs haplo-BM UCB vs haplo-PB |
1.44 1.86 |
1.14–1.82 1.39–2.50 |
0.002 < 0.0001 |
CMV serostatus, lymphoma subtype, and disease status |
OS UCB vs haplo-BM UCB vs haplo-PB |
1.55 1.59 |
1.19–2.03 1.15–2.20 |
0.001 0.005 |
Age, sex, CMV serostatus, lymphoma subtype, and disease status |
This analysis has shown UCB transplant leads to lower OS and PFS compared with haplo-HSCT, specifically in patients with lymphoma. The lower OS and PFS with UCB transplant were attributed to higher TRM and not relapse/progression. Additionally, outcome based on donor type was independent of other factors, such as disease type or status at transplant. Finally, there were no differences in PFS or OS comparing BM to PB as stem cell source for haplo-HSCT.
The authors recommend performing haplo-HSCT (BM or PB) for patients with HL and NHL when no HLA-matched donor can be found and conducting UCB only in cases where a haplo donor is not available. Future studies using UCB for transplantation should investigate strategies to lower the risk of GVHD, such as the use of PTCy.
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