Recent results of different haploidentical hematopoietic transplant protocols in adult acute leukemia patients
| Transplant protocol . | Patient age, median (range) . | Sample size and disease, no. (%) . | Disease status at transplant, no. (%) . | Incidence of GVHD, % . | Incidence of NRM, % . | Incidence of relapse, % . | Probability of survival, % . |
|---|---|---|---|---|---|---|---|
| Unmanipulated BM or G-CSF–mobilized PB graft with high-dose posttransplant cyclophosphamide*66 | NR (21-70) | 192 AML | CR1: 91 (47) | Acute grade II-IV GVHD: | 14-9† (at 3 years) | 44-58† (at 3 years) | Overall survival: 45-46† |
| CR2: 52 (27) | 16-19† | ||||||
| Relapse: 49 (26) | Chronic GVHD: 30-34† | Chronic GVHD-free/ | |||||
| (at 3 years) | leukemia-free survival: | ||||||
| 24-18† (at 3 years) | |||||||
| Unmanipulated G-CSF–mobilized PB graft with in vivo T-cell depletion69 | 40 (16-70) | 83 | CR1: 15 (18) | Acute grade II-IV GVHD: 20 | 18 | CR1: 27 | Leukemia-free survival: |
| AML: 52 (63) | CR ≥2: 19 (23) | Chronic GVHD: 34 | CR≥2: 32 | CR1: 60 | |||
| ALL: 16 (19) | Refractory disease: 34 (41) | Refractory disease: 79 | CR ≥2: 53 | ||||
| MDS: 15 (18) | Low-risk MDS: 6 (7) | MDS: 20 | Refractory disease: 9 | ||||
| High-risk MDS: 9 (11) | MDS: 53 | ||||||
| Unmanipulated G-CSF–primed BM and PB graft with in vivo T-cell depletion72 | 25 (3-57) | 756 | Standard risk‡: 484 (64) | Acute grade II-IV GVHD: 43 | 18% (at 3 years) | AML: 22 | Leukemia-free survival: |
| AML: 321 (42) | High risk§: 136 (18) | Chronic GVHD: 53 | ALL: 20 | AML: 64 | |||
| ALL: 299 (40) | First chronic phase CML: 77 (10) | (at 2 years) | CML: 9 (at 3 years) | ALL: 57 | |||
| CML: 136 (18) | Beyond first chronic phase CML: 59 (8) | CML: 73 (at 3 years) | |||||
| Unmanipulated BM and/or PB graft with in vivo T-cell depletion or high-dose posttransplant cyclophosphamide||99 | 42 (18-66) | 229 | CR1: 77 (34) | Acute grade II-IV GVHD: 32 | 28 (at 3 years) | CR1: 32 | Leukemia-free survival: |
| AML: 156 (68) | CR2: 56 (24) | Chronic GVHD: 34 | CR2: 24 | CR1: 44 | |||
| ALL: 73 (32) | Advanced disease (CR3/active disease): | (at 3 years) | Advanced disease: 61 | CR2: 42 | |||
| 96 (42) | (at 3 years) | Advanced disease: 12 | |||||
| (at 3 years) | |||||||
| Unmanipulated BM or PB graft with in vivo T-cell depletion or high-dose posttransplant cyclophosphamide¶100 | 32 (18-76) | 208 ALL | CR1: 90 (44) | Acute grade II-IV GVHD: 31 | CR1: 26 | CR1: 26 | Leukemia-free survival: |
| CR ≥2: 59 (28) | Chronic GVHD: 27 | CR ≥2: 36 | CR ≥2: 32 | CR1: 45 | |||
| Active disease: 59 (28) | Active disease: 35 | Active disease: 60 | CR≥2: 32 | ||||
| (at 2 years) | (at 2 years) | Active disease: 5 | |||||
| (at 2 years) | |||||||
| Ex vivo T cell–depleted G-CSF–mobilized PB graft with Treg/Tcon immunotherapy93-95 (Alessandra Carotti, Franca Falzetti, L.R., and A.V., unpublished data, June 30, 2016) | 38.5 (20-59) | 60 | CR1: 38 (63) | Acute grade II-IV GVHD: 15 | 35 (at 5 years) | 12 (at 5 years) | Leukemia-free survival: 53 |
| AML: 42 (70) | CR ≥2: 22 (37) | Chronic GVHD: 3 | Chronic GVHD-free/ | ||||
| ALL: 18 (30) | (at 5 years) | leukemia-free survival: 50 (at 5 years) | |||||
| Transplant protocol . | Patient age, median (range) . | Sample size and disease, no. (%) . | Disease status at transplant, no. (%) . | Incidence of GVHD, % . | Incidence of NRM, % . | Incidence of relapse, % . | Probability of survival, % . |
|---|---|---|---|---|---|---|---|
| Unmanipulated BM or G-CSF–mobilized PB graft with high-dose posttransplant cyclophosphamide*66 | NR (21-70) | 192 AML | CR1: 91 (47) | Acute grade II-IV GVHD: | 14-9† (at 3 years) | 44-58† (at 3 years) | Overall survival: 45-46† |
| CR2: 52 (27) | 16-19† | ||||||
| Relapse: 49 (26) | Chronic GVHD: 30-34† | Chronic GVHD-free/ | |||||
| (at 3 years) | leukemia-free survival: | ||||||
| 24-18† (at 3 years) | |||||||
| Unmanipulated G-CSF–mobilized PB graft with in vivo T-cell depletion69 | 40 (16-70) | 83 | CR1: 15 (18) | Acute grade II-IV GVHD: 20 | 18 | CR1: 27 | Leukemia-free survival: |
| AML: 52 (63) | CR ≥2: 19 (23) | Chronic GVHD: 34 | CR≥2: 32 | CR1: 60 | |||
| ALL: 16 (19) | Refractory disease: 34 (41) | Refractory disease: 79 | CR ≥2: 53 | ||||
| MDS: 15 (18) | Low-risk MDS: 6 (7) | MDS: 20 | Refractory disease: 9 | ||||
| High-risk MDS: 9 (11) | MDS: 53 | ||||||
| Unmanipulated G-CSF–primed BM and PB graft with in vivo T-cell depletion72 | 25 (3-57) | 756 | Standard risk‡: 484 (64) | Acute grade II-IV GVHD: 43 | 18% (at 3 years) | AML: 22 | Leukemia-free survival: |
| AML: 321 (42) | High risk§: 136 (18) | Chronic GVHD: 53 | ALL: 20 | AML: 64 | |||
| ALL: 299 (40) | First chronic phase CML: 77 (10) | (at 2 years) | CML: 9 (at 3 years) | ALL: 57 | |||
| CML: 136 (18) | Beyond first chronic phase CML: 59 (8) | CML: 73 (at 3 years) | |||||
| Unmanipulated BM and/or PB graft with in vivo T-cell depletion or high-dose posttransplant cyclophosphamide||99 | 42 (18-66) | 229 | CR1: 77 (34) | Acute grade II-IV GVHD: 32 | 28 (at 3 years) | CR1: 32 | Leukemia-free survival: |
| AML: 156 (68) | CR2: 56 (24) | Chronic GVHD: 34 | CR2: 24 | CR1: 44 | |||
| ALL: 73 (32) | Advanced disease (CR3/active disease): | (at 3 years) | Advanced disease: 61 | CR2: 42 | |||
| 96 (42) | (at 3 years) | Advanced disease: 12 | |||||
| (at 3 years) | |||||||
| Unmanipulated BM or PB graft with in vivo T-cell depletion or high-dose posttransplant cyclophosphamide¶100 | 32 (18-76) | 208 ALL | CR1: 90 (44) | Acute grade II-IV GVHD: 31 | CR1: 26 | CR1: 26 | Leukemia-free survival: |
| CR ≥2: 59 (28) | Chronic GVHD: 27 | CR ≥2: 36 | CR ≥2: 32 | CR1: 45 | |||
| Active disease: 59 (28) | Active disease: 35 | Active disease: 60 | CR≥2: 32 | ||||
| (at 2 years) | (at 2 years) | Active disease: 5 | |||||
| (at 2 years) | |||||||
| Ex vivo T cell–depleted G-CSF–mobilized PB graft with Treg/Tcon immunotherapy93-95 (Alessandra Carotti, Franca Falzetti, L.R., and A.V., unpublished data, June 30, 2016) | 38.5 (20-59) | 60 | CR1: 38 (63) | Acute grade II-IV GVHD: 15 | 35 (at 5 years) | 12 (at 5 years) | Leukemia-free survival: 53 |
| AML: 42 (70) | CR ≥2: 22 (37) | Chronic GVHD: 3 | Chronic GVHD-free/ | ||||
| ALL: 18 (30) | (at 5 years) | leukemia-free survival: 50 (at 5 years) | |||||
BM, bone marrow; CML, chronic myeloid leukemia; NR, not reported; PB, peripheral blood.
Graft source was bone marrow in 84% of patients and G-CSF–mobilized peripheral blood hematopoietic cells in 16% of patients.
Outcomes after myeloablative or reduced intensity conditioning regimens, respectively.
Standard risk: CR1 or CR2 at transplant, without Philadelphia chromosome.
High risk: CR ≥3 or nonremission at transplant, or acute leukemia with Philadelphia chromosome in any disease status at transplant.
Graft source was bone marrow in 44% of patients, G-CSF–mobilized peripheral blood hematopoietic cells in 53% of patients, and a combination of the two in 3% of patients. GVHD prophylaxis was based on in vivo T-cell depletion with anti–T-cell antibodies (75%) or posttransplant high-dose cyclophosphamide (13%) or other (12%).
Graft source was bone marrow in 44% of patients and G-CSF–mobilized peripheral blood hematopoietic cells in 56% of patients. GVHD prophylaxis was based on posttransplant high-dose cyclophosphamide (52%) or in vivo T-cell depletion with antithymocyte globulin (48%).