Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma; Insights into Its Potential Role in the Era of New Immunotherapeutic and Targeted Therapies: The GETH/GELTAMO Experience
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Patient Eligibility
2.2. Data Recovery and Study Definitions
2.3. Statistical Analysis
3. Results
3.1. Patient and Allo-SCT Characteristics
3.2. Main Outcome Data
3.3. GVHD and NRM
3.4. Survival Analysis
3.5. Impact in Results of Allo-SCT Candidates’ Selection along Decades
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics at Diagnosis | N (%) | Missing Data (%) |
---|---|---|
Median age, years (range) | 52 (31–67) | 0 (0%) |
Sex (M/F) | 108 (80%)/27 (20%) | 0 (0%) |
Ann Arbor stage: | 2 (1%) | |
I–II | 8 (6%) | - |
III–IV | 125 (94%) | - |
B-symptoms: | 44 (38%) | 20 (15%) |
CNS involvement: | 2 (2%) | 7 (5%) |
Bone marrow involvement: | 98 (75%) | 4 (3%) |
Number of extranodal sites: | 7 (5%) | |
0–1 | 81 (63%) | - |
>1 | 47 (37%) | - |
Mantle cell lymphoma histology: | 33 (24%) | |
Indolent [17] | 7 (7%) | - |
Classic | 67 (66%) | - |
Blastic | 28 (27%) | - |
Characteristics at allo-SCT | - | |
Median previous lines of therapy (range) | 2 (1–8) | 2 (1%) |
Previous ASCT | 66 (49%) | 0 (0%) |
Previous ibrutinib | 19 (14%) | 2 (1%) |
Median months from diagnosis to allo-SCT (range) | 33 (3–164) | 0 (0%) |
Median age, years (range) | 56 (32–70) | 0 (0%) |
Age >60 years | 36 (27%) | 0 (0%) |
Donor type: | 0 (0%) | |
HLA-id sibling | 74 (55%) | - |
HLA-id unrelated | 29 (21%) | - |
Haploidentical | 18 (13%) | - |
Mismatch unrelated | 14 (10%) | - |
Median donor age (range) | 46 (19–72) | 2 (1%) |
Donor sex: | 0 (0%) | |
Male | 82 (61%) | - |
Female | 53 (39%) | - |
ECOG PS: | 12 (9%) | |
0 | 74 (60%) | - |
1 | 43 (35%) | - |
2–4 | 6 (5%) | - |
HCT-CI: | 11 (8%) | |
0–1 | 70 (56%) | - |
2 | 28 (23%) | - |
≥3 | 26 (21%) | - |
Disease status: | 1 (1%) | |
CR | 86 (64%) | - |
PR | 35 (26%) | - |
SD/PD | 13 (10%) | - |
NE | 1 (1%) | - |
Conditioning regimen: | 0 (0%) | |
Myeloablative | 20 (15%) | - |
RIC | 115 (85%) | - |
Myeloablative conditioning: | 0 (0%) | |
Cy + TBI | 10 (50%) | - |
FLUBU | 5 (25%) | - |
FLUMEL | 1 (5%) | - |
BEAM | 1 (5%) | - |
Other | 3 (15%) | - |
RIC: | 0 (0%) | |
FLUMEL | 90 (78%) | - |
FLUBU | 15 (13%) | - |
Cy + TBI | 4 (4%) | - |
Other | 6 (5%) | - |
GVHD prophylaxis: | 0 (0%) | |
CsA/Tacro-MTX | 45 (33%) | - |
CsA /Tacro-MMF | 31 (23%) | - |
Timoglobulin based prophylaxis | 24 (18%) | - |
Tacro-sirolimus | 19 (14%) | - |
Cy-post | 12 (9%) | - |
Other | 4 (3%) | - |
CMV recipient/donor relation: | 2 (1%) | |
R−/D− | 12 (9%) | - |
R−/D+ | 11 (8%) | - |
R+/D− | 35 (26%) | - |
R+/D− | 75 (56%) | - |
Stem cell source: | 1 (1%) | |
PB | 127 (95%) | - |
BM | 5 (4%) | - |
UCB * | 2 (2%) | - |
Median CD34 + cells (range) (×106/kg) | 5.1 (0.1–18.1) | 5 (4%) |
Characteristics | Day100-NRM (%) | p |
---|---|---|
Age at allo-SCT: | 1 | |
18–56 | 14 (20%) | |
>56 years | 12 (19%) | |
Months from diagnosis to allo-SCT: | 0.51 | |
0–33 | 11 (16%) | |
>33 | 15 (22%) | |
Previous lines: | 0.65 | |
0–2 | 13 (17%) | |
>2 | 12 (21%) | |
Previous ASCT: | 0.008 | |
No | 7 (10%) | |
Yes | 19 (29%) | |
Donor type: | 0.38 | |
HLA-id sibling | 12 (16%) | |
HLA-id unrelated | 5 (17%) | |
Mismatch unrelated | 5 (36%) | |
Haploidentical | 4 (22%) | |
Donor type: | 0.2 | |
HLA-id | 17 (16%) | |
Mismatch related | 4 (22%) | |
Mismatch unrelated | 5 (36%) | |
Donor age: | 0.38 | |
18–46 | 15 (22%) | |
>46 | 10 (15%) | |
Donor sex: | 0.82 | |
Male | 15 (18%) | |
Female | 11 (21%) | |
ECOG PS at allo-SCT | 0.31 | |
0–1 | 21 (18%) | |
2–4 | 2 (33%) | |
Pretransplant HCT-CI: | 0.58 | |
0–2 | 18 (18%) | |
≥3 | 6 (23%) | |
Conditioning regimen: | 0.76 | |
Myeloablative | 3 (15%) | |
RIC | 23 (20%) | |
GVHD prophylaxis: | 0.25 | |
CsA/Tacro-MTX | 20 (22%) | |
Other | 6 (13%) | |
CMV recipient/donor relation: | 0.26 | |
R−/D− | 1 (8%) | |
R−/D+ | 2 (18%) | |
R+/D− | 4 (11%) | |
R+/D− | 19 (25%) | |
Stem cell source: | 0.54 | |
PB | 24 (19%) | |
BM | 1 (20%) | |
UCB | 1 (50%) | |
CD34+ infused cells (range) (×106/kg): | 1 | |
0.1–5.1 | 13 (20%) | |
>5.1 | 13 (20%) | |
aGVHD: | <0.001 | |
No aGVHD or grade 1–2 | 11 (11%) | |
Grade 3–4 | 15 (43%) |
Univariate Analysis | ||||
---|---|---|---|---|
Characteristics | 5y-EFS (95% CI) | p | 5y-OS (95% CI) | p |
Age at allo-SCT: | 0.7 | 0.66 | ||
0–60 | 50% (40–60) | 52% (42–63) | ||
>60 | 39% (21–57) | 42% (24–60) | ||
Median months from diagnosis to allo-SCT | 0.53 | 0.77 | ||
0–33 | 51% (39–63) | 52% (40–64) | ||
>33 | 44% (31–56) | 47% (34–60) | ||
Donor type: | 0.032 | 0.2 | ||
HLA-id sibling | 52% (40–64) | 55% (43–67) | ||
HLA-id non-related | 50% (31–69) | 49% (30–68) | ||
Mismatch non-related | 21% (0–45) | 35% (7–63) | ||
Haploidentical | 44% (21–67) | 42% (17–66) | ||
Mismatch: | 0.018 | 0.044 | ||
Yes | 35% (18–52) | 39% (20–57) | ||
No | 51% (41–61) | 53% (43–63) | ||
ECOG PS at allo-SCT: | 0.035 | 0.021 | ||
0–1 | 51% (42–60) | 54% (45–63) | ||
2–4 | 0% (NA) | 0% (NA) | ||
HCT-CI: | 0.41 | 0.42 | ||
0–2 | 49% (39–60) | 52% (42–63) | ||
3 or more | 31% (13–50) | 35% (16–54) | ||
Previous lines of therapy: | 0.11 | 0.4 | ||
1–2 | 55% (43–66) | 55% (43–66) | ||
>2 | 37% (24–50) | 42% (28–56) | ||
Previous ASCT: | 0.061 | 0.02 | ||
Yes | 39% (27–52) | 39% (25–52) | ||
No | 55% (43–67) | 59% (48–71) | ||
Previous ibrutinib: | 0.66 | 0.89 | ||
Yes | 44% (18–69) | 28% (0–69) | ||
No | 48% (39–57) | 50% (41–60) | ||
Conditioning regimen: | 0.69 | 0.99 | ||
Myeloablative | 48% (26–70) | 48% (25–70) | ||
RIC | 47% (38–57) | 50% (40–60) | ||
Response pre-allo-SCT: | 0.005 | 0.004 | ||
CR | 54% (43–65) | 58% (47–69) | ||
PR | 40% (23–57) | 43% (25–60) | ||
SD/PD | 15% (0–35) | 15% (0–35) | ||
GVHD prophylaxis: | 0.021 | 0.008 | ||
CsA/Tacro-MTX | 62% (47–76) | 66% (52–80) | ||
Other | 40% (30–51) | 41% (30–52) | ||
Time-period: | 0.02 | 0.023 | ||
1995–2005 | 69% (51–87) | 69% (51–87) | ||
2006–2020 | 42% (32–52) | 45% (35–55) | ||
Time-period: | 0.023 | 0.03 | ||
1995–2005 | 69% (51–87) | 69% (51–87) | ||
2006–2011 | 33% (20–47) | 38% (24–52) | ||
2012–2020 | 49% (37–62) | 50% (37–64) | ||
Time-dependent variables (univariate) | EFS | p | OS | p |
HR (95% CI) | HR (95% CI) | |||
Grade 3–4 aGVHD | 5.1 (3.2–8.1) | <0.001 | 6 (3.7–9.8) | <0.001 |
Chronic GVHD | 1 (0.5–2) | 0.97 | 1 (0.5–2) | 0.92 |
Multivariate analysis | ||||
Grade 3–4 aGVHD: | 7.6 (4.5–12.8) | <0.001 | 8.9 (5.1–15.3) | <0.001 |
Mismatch non-related: | 3 (1.5–6.2) | 0.002 | - | - |
Time-period 2006–2020: | 2.7 (1.1–6.4) | 0.023 | 3.2 (1.3–8) | 0.014 |
Characteristics | Global Series (N = 135) | 2006–2020 | 1995–2005 | p |
---|---|---|---|---|
(N = 109) | (N = 26) | |||
Median age at allo-SCT, years (range) | 56 (32–70) | 57 (32–70) | 52 (34–68) | 0.047 |
Median months diagnosis to allo-SCT (range) | 33 (3–164) | 39 (3–164) | 13 (5–84) | 0.001 |
Frontline therapy cytarabine-based | 93 (70%) | 76 (70%) | 17 (68%) | 0.81 |
More than 33 months from diagnosis to allo-SCT | 67 (50%) | 46 (42%) | 5 (19%) | <0.001 |
Donor type: | <0.001 | |||
HLA-id sibling | 74 (55%) | 50 (46%) | 24 (92%) | |
HLA-id non-related | 29 (21%) | 28 (26%) | 1 (4%) | |
Haploidentical | 18 (13%) | 18 (16%) | 0 (0%) | |
Mismatch non-related | 14 (10%) | 13 (12%) | 1 (4%) | |
ECOG PS at allo-SCT: | 1 | |||
0–1 | 117 (95%) | 98 (95%) | 19 (95%) | |
2–4 | 6 (5%) | 5 (5%) | 1 (5%) | |
HCT-CI at allo-SCT: | 0.11 | |||
0–1 | 70 (56%) | 56 (53%) | 14 (78%) | |
2 | 28 (23%) | 25 (24%) | 3 (17%) | |
3 or more | 26 (21%) | 25 (24%) | 1 (6%) | |
>2 previous lines: | 57 (43%) | 52 (48%) | 5 (20%) | 0.013 |
Previous ASCT: | 66 (49%) | 61 (56%) | 5 (19%) | 0.001 |
Response pre-allo-SCT: | 0.92 | |||
CR | 86 (64%) | 70 (64%) | 16 (61%) | |
PR | 35 (26%) | 28 (26%) | 7 (27%) | |
SD/PD | 13 (10%) | 101 (9%) | 3 (11%) | |
NE | 1 (1%) | 1 (1%) | ||
Conditioning: | 0.067 | |||
Myeloablative | 20 (15%) | 13 (12%) | 7 (27%) | |
RIC | 115 (85%) | 96 (88%) | 19 (73%) | |
GVHD prophylaxis: | <0.001 | |||
CsA/Tacro-MTX | 45 (33%) | 81 (74%) | 9 (35%) | |
Other | 90 (67%) | 28 (26%) | 17 (65%) | |
Donor median age (range) | 46 (19–72) | 45 (19–72) | 53 (25–70) | 0.052 |
Stem cell source: | 0.26 | |||
PB | 127 (95%) | 104 (96%) | 23 (88%) | |
BM | 5 (4%) | 3 (3%) | 2 (8%) | |
UCB | 2 (2%) | 1 (1%) | 1 (4%) | |
Median de CD34 + cells (range) (×106/kg) | 5.1 (0.1–18.1) | 5.1 (0.1–13) | 4.3 (2.1–18.1) | 0.45 |
aGVHD at + 100: | 74 (55%) | 70 (64%) | 13 (50%) | 0.5 |
aGVHD at + 100: | 0.37 | |||
No aGVHD | 60 (45%) | 39 (36%) | 13 (50%) | |
1–2 | 42 (31%) | 38 (35%) | 8 (31%) | |
3–4 | 32 (24%) | 32 (29%) | 5 (19%) | |
Chronic GVHD (%): | 48 (36%) | 36 (33%) | 12 (46%) | 0.26 |
Chronic GVHD (%): | 0.59 | |||
No | 87 (64%) | 73 (68%) | 14 (54%) | |
Mild | 17 (13%) | 14 (13%) | 3 (12%) | |
Moderate | 15 (11%) | 11 (10%) | 4 (16%) | |
Severe | 14 (10%) | 10 (9%) | 4 (16%) | |
Overall NRM (%): | 61 (45%) | 54 (49%) | 7 (27%) | 0.048 |
NRM at +100 (%): | 27 (20%) | 24 (22%) | 3 (11%) | 0.28 |
NRM at 1 year (%) | 45 (33%) | 40 (37%) | 5 (19%) | 0.11 |
Causes of death: | 0.16 | |||
aGVHD | 32 (45%) | 30 (49%) | 2 (20%) | |
Infection | 15 (21%) | 11 (18%) | 4 (40%) | |
Lymphoma | 12 (17%) | 9 (15%) | 3 (30%) | |
Other | 12 (17%) | 11 (18%) | 1 (10%) | |
Response post-allo-SCT: | 0.12 | |||
CR | 110 (81%) | 88 (81%) | 22 (85%) | |
PR | 6 (4%) | 6 (5%) | 0 (0%) | |
SD/PD | 6 (4%) | 4 (4%) | 2 (8%) | |
NE | 13 (10%) | 11 (10%) | 2 (8%) |
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Gutierrez, A.; Bento, L.; Novelli, S.; Martin, A.; Gutierrez, G.; Queralt Salas, M.; Bastos-Oreiro, M.; Perez, A.; Hernani, R.; Cruz Viguria, M.; et al. Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma; Insights into Its Potential Role in the Era of New Immunotherapeutic and Targeted Therapies: The GETH/GELTAMO Experience. Cancers 2022, 14, 2673. https://doi.org/10.3390/cancers14112673
Gutierrez A, Bento L, Novelli S, Martin A, Gutierrez G, Queralt Salas M, Bastos-Oreiro M, Perez A, Hernani R, Cruz Viguria M, et al. Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma; Insights into Its Potential Role in the Era of New Immunotherapeutic and Targeted Therapies: The GETH/GELTAMO Experience. Cancers. 2022; 14(11):2673. https://doi.org/10.3390/cancers14112673
Chicago/Turabian StyleGutierrez, Antonio, Leyre Bento, Silvana Novelli, Alejandro Martin, Gonzalo Gutierrez, Maria Queralt Salas, Mariana Bastos-Oreiro, Ariadna Perez, Rafael Hernani, Maria Cruz Viguria, and et al. 2022. "Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma; Insights into Its Potential Role in the Era of New Immunotherapeutic and Targeted Therapies: The GETH/GELTAMO Experience" Cancers 14, no. 11: 2673. https://doi.org/10.3390/cancers14112673