Selected articles from 1996 onward using second allogeneic hematopoietic cell transplantation (HCT) to treat relapse.
| Author . | Diseases . | Status at 2nd HCT . | 2nd HCT conditioning . | 2nd HCT donor . | Same donor used . | NRM or TRM . | DFS . | OS . | Comments . |
|---|---|---|---|---|---|---|---|---|---|
| 2CDA indicates cladribine; Alem, alemtuzumab; Ara-C, cytarabine; ATG, antithymocyte globulin; Auto, autograft; ALL, acute lymphoblastic leukemia; AML, acute myelogenous leukemia; ANLL, acute nonlymphocytic leukemia; ceGVHD, chronic extensive GVHD; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; Dauno, daunorubicin; FLAG, fludarbine/cytarabine/granulocyte colony stimulating factor; Flu, fludarabine; IBMTR, International Bone Marrow Transplant Registry; Ida, Idarubicin; IS, immunosuppression; JMML, juvenile myelomonocytic leukemia; MDS, myelodysplastic syndrome; Bu, busulfan; Cy, cyclophosphamide; Mel, melphalan; MMRD, HLA-mismatched related donor; MP, methylprednisolone, MPD; myeloproliferative disease; MRD, HLA-matched related donor; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; NR, Not in remission; PR, partial response; RAEBt, refractory anemia with excess blasts in transformation; RIT, reduced-intensity transplant; thio, thiotepa; URD, HlA-matched unrelated donor; VP16, etoposide | |||||||||
| Chiang 19961 n = 23 | CML (11); acute leukemia (7); lymphoma (4); MDS (1) | Not stated | Bu/Cy (23) | MRD (18); MMURD (4); Auto (1) | 13 (57%) | 12 of 23 | 38% at 3 y | 43% at 3 y | 8 of 23 pts received autos for 1st HCT. |
| Bosi 19972 n = 38 | AML (21); ALL (17) | CR (24); Relapse (14) | TBI-based (14); non-TBI based (24) | MRD (38) | 34 (89%) | 11 of 38 (28% at 3 y) | 42% at 3 y | Not stated | 13 Italian BMT centers; Remission after 2nd HCT longer than 1st; AML did better. |
| Kishi 19973 n = 66 | ANLL (29); ALL (27); CML (6); MDS (4) | CR (30); NR (24) | Multiple high-dose regimens (Cy, TBI, Bu, Ara-C, VP16, Mel) | Sibs (59); syngeneic twin 3); other relatives (4) | 55 (83%) | 14 of 66 at 3 mo | 28% 2 y; 15% at 4 y CR/NR: 38/23% 1 y; 34/23% 2 y; 30/0% 4 y | Not stated | Survey sent to 24 centers in Japan |
| Mehta 19974 n = 23 | Acute leukemias (23) | CR (7); PR (5); Untreated relapse (8); Refractory (3) | Mel ± TBI (6); Bu/Cy (1); Cy/TBI (16) | Unknown | 22 (96%) | 38.3% at 2 y | 0 of 23 | 1 of 23 | 23 of 114 pts relapsed after primary HCT. 17 of 23 pts relapsed after 2nd HCT. |
| Blau 20005 n = 27 | AML (17); ALL (6); CML (4) | CR (5); PR (7); Refractory relapse (7); Untreated relapse (8) | TBI/Cy(11); Bu/VP16 (8); Bu/Cy (6); Cy/MP/ATG (2) | MRD (11); URD (16) | 11 (41%) | 7 of 27 200 d | 8 of 27 (7 pts had prior auto; 1 pt with prior allo) | 29% (43% for pts with 1st with auto) | 16 of 27 pts received autos for 1st HCT |
| Michallet 20006 n = 150 | AML (61); ALL (47); CML (42) | CR (60); Chemosensitive (8); Untreated relapse (27); Refractory relapse (13); CP (17); accelerated (13); blast (12) | TBI-based (25%); Non-TBI (75%) | Syngeneic twin (7); MRD (133); MMRD (3); Pheno-identical donor (2); URD (5) | 83% | 45±9% | 30±8% at 5 y | 32±8% at 5 y | Survey sent to 31 centers in France. Risk of relapse 44±12% |
| Bosi 20017 n = 170 | AML (85); ALL (83); AUL (2) | CR (81); Relapse (86); Primary refractory (3) | TBI-based (38); Non-TBI (130) | MRD (154); Syngeneic twin (7); MMRD (6); URD (3) | 154 (91%) | 68 of 170 (46% at 5 y) | 25% at 5 y (20% if relapsed; 13% if refractory) | 26% at 5 y (16% if relapse/refractory) | Retrospective review of 56 European centers; Relapse rate 59% at 5 y |
| Keil 20018 n = 5 | AML (4); ALL (1) | CR (1); Untreated relapse (3); Refractory relapse (1) | Not stated | Not stated | Not stated | 5 of 5 | 3 of 5 with initial CR | 0% | 5 of 47 pts were given 2nd HCT. The remaining 42 underwent other therapies (DLI, chemo, withdrawal IS) |
| Pawson 20019 n = 14 | AML (7) ALL (5) RAEBt(2) | CR (3); Relapse (11) | FLAG ±Ida | MRD (13); 1 ant MM sib (1) | 14 (100%) | 0 of 14 | 26% at 58 mo | 60% at 58 mo | 10 of 14 pts relapsed (4 despite ceGVHD) |
| Tomonari 200210 n = 16 | AML (7) ALL (8) CML (1) | CR (7); Relapse (7); Aplasia (2) | Dauno (1), Bu/Cy±VP16 (7); TBI/Ara-C (4); TBI/VP16 (2); Cy/VP16 (1); none (1) | MRD (13); MM sib (2); URD (1) | 14 (88%) | 4 of 16 100 d | 5 of 16 | 44% 1 y 31% 4 y (14% OS 4 y if in relapse at 2nd HCT) | 3 pts received DLI after 2nd HCT |
| Meshinchi 200311 n = 25 | AML (25) | CR (10) Relapse (15) | Cy/TBI ± ATG | MRD (12), MMR (9), URD (4) | Not stated | 5 of 25 | 44% 10 y (70% if in remission; 27% if in relapse) | 88% 100 d 56% 1 yr 48% 10 y | 11 of 25 pts received autos for 1st HCT |
| Chang 200412 n = 5 | JMML (5) | Relapse (5) | TBI-based (3); non-TBI (1); unknown (1) | MRD (3); 1 ant MM sib (1); Unknown (1) | 4 (1 unknown) | 1 of 5 | 3 of 5 | 3 of 5 | Case (1) + lit search (4) |
| Eapen 200413 n = 279 | AML (125); ALL (72); CML (82) | CR (144); Relapse (135) | Myeloablative with TBI (90) and w/o TBI (144); RIT with TBI (1) and w/o TBI (44) | Unknown | 238 (85%) | 26% 1 y; 30% 5 y | 38% 1y; 28% 5 y | 41% 1 y; 28% 5 y | IBMTR study; 36% relapse at 1 y, 42% 5 y; no advantage seen when using different MRD |
| Duus 200514 n = 6 | CML (2); CLL (1); AML (1); MDS (1); NHL (1) | CR (1); PR (1); CP (1); AP (1); Refractory relapse (1); Untreated relapse (1) | Bu/Cy (2); Cy/TBI ±VP16 (3); TBI 2Gy/ATG (1) | MRD (1); URD (4); 5/6 MRD (1) | 0 (0%) | 0 of 6 | 5 of 6 achieved CR | 67% median 23 months | |
| Pollyea 200715 n = 13 | AML (12) MDS(1) | Unknown due to no eval after re-induction (4); CR (2); Relapse (7) | Thio/Bu/Cy ±Alem; Bu/Cy; 2CDA; T BI/Thio/Flu; Flu/Bu/Alem | MRD (14); URD (11) [No more than 1 antigen/allele MM] | 13 (100%) | 2 of 13 | 10 of 13 with initial CR 2 of 13 with durable CR | 2 of 13 | 1 pt received DLI after 2nd HCT |
| Shaw 200816 n = 71 | AML (26); ALL (14); MDS (9); CML (7); MPD (3); MM (2) | CR/PR (33); Relapse (36); Unknown (2) | FLAG±Ida (26) Flu/Mel or Bu (25); Flu/low-dose TBI (6); Other Flu (4); Other non-Flu (8); Unknown (2) | MRD (49); URD (18); Other related (4) | 56 (80%) | 15% 100 d; 23% 1 y | 33% 1 y 22% 2 y | 42% 1 y 28% 2 y | UK Study-all received RIT conditioning for 2nd HCT; 48% relapse at 1 yr, 56% relapse at 2 yrs |
| Author . | Diseases . | Status at 2nd HCT . | 2nd HCT conditioning . | 2nd HCT donor . | Same donor used . | NRM or TRM . | DFS . | OS . | Comments . |
|---|---|---|---|---|---|---|---|---|---|
| 2CDA indicates cladribine; Alem, alemtuzumab; Ara-C, cytarabine; ATG, antithymocyte globulin; Auto, autograft; ALL, acute lymphoblastic leukemia; AML, acute myelogenous leukemia; ANLL, acute nonlymphocytic leukemia; ceGVHD, chronic extensive GVHD; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; Dauno, daunorubicin; FLAG, fludarbine/cytarabine/granulocyte colony stimulating factor; Flu, fludarabine; IBMTR, International Bone Marrow Transplant Registry; Ida, Idarubicin; IS, immunosuppression; JMML, juvenile myelomonocytic leukemia; MDS, myelodysplastic syndrome; Bu, busulfan; Cy, cyclophosphamide; Mel, melphalan; MMRD, HLA-mismatched related donor; MP, methylprednisolone, MPD; myeloproliferative disease; MRD, HLA-matched related donor; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; NR, Not in remission; PR, partial response; RAEBt, refractory anemia with excess blasts in transformation; RIT, reduced-intensity transplant; thio, thiotepa; URD, HlA-matched unrelated donor; VP16, etoposide | |||||||||
| Chiang 19961 n = 23 | CML (11); acute leukemia (7); lymphoma (4); MDS (1) | Not stated | Bu/Cy (23) | MRD (18); MMURD (4); Auto (1) | 13 (57%) | 12 of 23 | 38% at 3 y | 43% at 3 y | 8 of 23 pts received autos for 1st HCT. |
| Bosi 19972 n = 38 | AML (21); ALL (17) | CR (24); Relapse (14) | TBI-based (14); non-TBI based (24) | MRD (38) | 34 (89%) | 11 of 38 (28% at 3 y) | 42% at 3 y | Not stated | 13 Italian BMT centers; Remission after 2nd HCT longer than 1st; AML did better. |
| Kishi 19973 n = 66 | ANLL (29); ALL (27); CML (6); MDS (4) | CR (30); NR (24) | Multiple high-dose regimens (Cy, TBI, Bu, Ara-C, VP16, Mel) | Sibs (59); syngeneic twin 3); other relatives (4) | 55 (83%) | 14 of 66 at 3 mo | 28% 2 y; 15% at 4 y CR/NR: 38/23% 1 y; 34/23% 2 y; 30/0% 4 y | Not stated | Survey sent to 24 centers in Japan |
| Mehta 19974 n = 23 | Acute leukemias (23) | CR (7); PR (5); Untreated relapse (8); Refractory (3) | Mel ± TBI (6); Bu/Cy (1); Cy/TBI (16) | Unknown | 22 (96%) | 38.3% at 2 y | 0 of 23 | 1 of 23 | 23 of 114 pts relapsed after primary HCT. 17 of 23 pts relapsed after 2nd HCT. |
| Blau 20005 n = 27 | AML (17); ALL (6); CML (4) | CR (5); PR (7); Refractory relapse (7); Untreated relapse (8) | TBI/Cy(11); Bu/VP16 (8); Bu/Cy (6); Cy/MP/ATG (2) | MRD (11); URD (16) | 11 (41%) | 7 of 27 200 d | 8 of 27 (7 pts had prior auto; 1 pt with prior allo) | 29% (43% for pts with 1st with auto) | 16 of 27 pts received autos for 1st HCT |
| Michallet 20006 n = 150 | AML (61); ALL (47); CML (42) | CR (60); Chemosensitive (8); Untreated relapse (27); Refractory relapse (13); CP (17); accelerated (13); blast (12) | TBI-based (25%); Non-TBI (75%) | Syngeneic twin (7); MRD (133); MMRD (3); Pheno-identical donor (2); URD (5) | 83% | 45±9% | 30±8% at 5 y | 32±8% at 5 y | Survey sent to 31 centers in France. Risk of relapse 44±12% |
| Bosi 20017 n = 170 | AML (85); ALL (83); AUL (2) | CR (81); Relapse (86); Primary refractory (3) | TBI-based (38); Non-TBI (130) | MRD (154); Syngeneic twin (7); MMRD (6); URD (3) | 154 (91%) | 68 of 170 (46% at 5 y) | 25% at 5 y (20% if relapsed; 13% if refractory) | 26% at 5 y (16% if relapse/refractory) | Retrospective review of 56 European centers; Relapse rate 59% at 5 y |
| Keil 20018 n = 5 | AML (4); ALL (1) | CR (1); Untreated relapse (3); Refractory relapse (1) | Not stated | Not stated | Not stated | 5 of 5 | 3 of 5 with initial CR | 0% | 5 of 47 pts were given 2nd HCT. The remaining 42 underwent other therapies (DLI, chemo, withdrawal IS) |
| Pawson 20019 n = 14 | AML (7) ALL (5) RAEBt(2) | CR (3); Relapse (11) | FLAG ±Ida | MRD (13); 1 ant MM sib (1) | 14 (100%) | 0 of 14 | 26% at 58 mo | 60% at 58 mo | 10 of 14 pts relapsed (4 despite ceGVHD) |
| Tomonari 200210 n = 16 | AML (7) ALL (8) CML (1) | CR (7); Relapse (7); Aplasia (2) | Dauno (1), Bu/Cy±VP16 (7); TBI/Ara-C (4); TBI/VP16 (2); Cy/VP16 (1); none (1) | MRD (13); MM sib (2); URD (1) | 14 (88%) | 4 of 16 100 d | 5 of 16 | 44% 1 y 31% 4 y (14% OS 4 y if in relapse at 2nd HCT) | 3 pts received DLI after 2nd HCT |
| Meshinchi 200311 n = 25 | AML (25) | CR (10) Relapse (15) | Cy/TBI ± ATG | MRD (12), MMR (9), URD (4) | Not stated | 5 of 25 | 44% 10 y (70% if in remission; 27% if in relapse) | 88% 100 d 56% 1 yr 48% 10 y | 11 of 25 pts received autos for 1st HCT |
| Chang 200412 n = 5 | JMML (5) | Relapse (5) | TBI-based (3); non-TBI (1); unknown (1) | MRD (3); 1 ant MM sib (1); Unknown (1) | 4 (1 unknown) | 1 of 5 | 3 of 5 | 3 of 5 | Case (1) + lit search (4) |
| Eapen 200413 n = 279 | AML (125); ALL (72); CML (82) | CR (144); Relapse (135) | Myeloablative with TBI (90) and w/o TBI (144); RIT with TBI (1) and w/o TBI (44) | Unknown | 238 (85%) | 26% 1 y; 30% 5 y | 38% 1y; 28% 5 y | 41% 1 y; 28% 5 y | IBMTR study; 36% relapse at 1 y, 42% 5 y; no advantage seen when using different MRD |
| Duus 200514 n = 6 | CML (2); CLL (1); AML (1); MDS (1); NHL (1) | CR (1); PR (1); CP (1); AP (1); Refractory relapse (1); Untreated relapse (1) | Bu/Cy (2); Cy/TBI ±VP16 (3); TBI 2Gy/ATG (1) | MRD (1); URD (4); 5/6 MRD (1) | 0 (0%) | 0 of 6 | 5 of 6 achieved CR | 67% median 23 months | |
| Pollyea 200715 n = 13 | AML (12) MDS(1) | Unknown due to no eval after re-induction (4); CR (2); Relapse (7) | Thio/Bu/Cy ±Alem; Bu/Cy; 2CDA; T BI/Thio/Flu; Flu/Bu/Alem | MRD (14); URD (11) [No more than 1 antigen/allele MM] | 13 (100%) | 2 of 13 | 10 of 13 with initial CR 2 of 13 with durable CR | 2 of 13 | 1 pt received DLI after 2nd HCT |
| Shaw 200816 n = 71 | AML (26); ALL (14); MDS (9); CML (7); MPD (3); MM (2) | CR/PR (33); Relapse (36); Unknown (2) | FLAG±Ida (26) Flu/Mel or Bu (25); Flu/low-dose TBI (6); Other Flu (4); Other non-Flu (8); Unknown (2) | MRD (49); URD (18); Other related (4) | 56 (80%) | 15% 100 d; 23% 1 y | 33% 1 y 22% 2 y | 42% 1 y 28% 2 y | UK Study-all received RIT conditioning for 2nd HCT; 48% relapse at 1 yr, 56% relapse at 2 yrs |