Second unmanipulated allogeneic transplantation could be used as a salvage option for patients with relapsed acute leukemia post-chemotherapy plus modified donor lymphocyte infusion
1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China 2. National Clinical Research Center for Hematologic Disease, Beijing 100044, China 3. Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China 4. Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China 5. Peking-Tsinghua Center for Life Sciences, Beijing 100044, China
Relapse is the main problem after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The outcome of a second allo-HSCT (HSCT2) for relapse post-HSCT has shown promising results in some previous studies. However, little is known about the efficacy of HSCT2 in patients with relapsed/refractory acute leukemia (AL) post-chemotherapy plus modified donor lymphocyte infusion (post-Chemo+m-DLI) after the first allo-HSCT (HSCT1). Therefore, we retrospectively analyzed the efficacy of HSCT2 in 28 patients with relapsed/refractory AL post-Chemo+m-DLI in our center. With a median follow-up of 918 (457–1732) days, 26 patients (92.9%) achieved complete remission, and 2 patients exhibited persistent disease. The probabilities of overall survival (OS) and disease-free survival (DFS) 1 year after HSCT2 were 25.0% and 21.4%, respectively. The cumulative incidences of nonrelapse mortality on day 100 and at 1 year post-HSCT2 were 7.1%±4.9% and 25.0%±8.4%. The cumulative incidences of relapse were 50.0%±9.8% and 53.5%±9.9% at 1 and 2 years post-HSCT2, respectively. Risk stratification prior to HSCT1 and percentage of blasts before HSCT2 were independent risk factors for OS post-HSCT2, and relapse within 6 months post-HSCT1 was an independent risk factor for DFS and relapse post-HSCT2. Our findings suggest that HSCT2 could be a salvage option for patients with relapsed AL post-Chemo+m-DLI.
. [J]. Frontiers of Medicine, 2021, 15(5): 728-739.
Tingting Han, Yuqian Sun, Yang Liu, Chenhua Yan, Yu Wang, Lanping Xu, Kaiyan Liu, Xiaojun Huang, Xiaohui Zhang. Second unmanipulated allogeneic transplantation could be used as a salvage option for patients with relapsed acute leukemia post-chemotherapy plus modified donor lymphocyte infusion. Front. Med., 2021, 15(5): 728-739.
Risk stratification before HSCT1, n (%) High risk Standard risk
16 (57.1%) 12 (42.9%)
Disease status before HSCT1, n (%) CR NR
23 (82.1%) 5 (17.9%)
Donor for HSCT1, n (%) MSD Haplo-donor URD
15 (53.6%) 11 (39.3%) 2 (7.1%)
Conditioning for HSCT1, n (%) BU/CY+ ATG BU/CY TBI/CY
13 (46.4%) 14 (50.0%) 1 (3.6%)
Sex match (donor/recipient) , n (%) Female–female Female–male Male–male Male–female
4 (14.3%) 7 (25.0%) 13 (46.4%) 4 (14.3%)
a-GVHD, n (%) Grade 1–2 Grade 3–4
7 (25.0%) 0
c-GVHD, n (%) Mild Moderate Severe
4 (14.3%) 3 (10.7%) 0
Duration of remission after HSCT1, n (%) ?6 months ≥6 months
9 (32.1%) 19 (67.9%)
Relapse, n (%) Marrow relapse Marrow+ extramedullary relapse
26 (92.9%) 2 (7.1%)
Tab.1
Fig.2
Variable
HSCT2 (N=28)
Time between HSCT1 and HSCT2, day
360.5 (121–1890)
Time from relapse to HSCT2, day
146.5 (55–1070)
Percentage of blast before HSCT2
15% (6%–92%)
Duration from HSCT1 to HSCT2, n (%) ≤12 months >12 months
13 (46.4%) 15 (53.6%)
Patient age at HSCT2, year
25.5 (3–53)
Donor age at HSCT2, year, n (%) ≤30 years 30–45 years ≥45 years
39 (17–57) 10 (35.7%) 13 (46.4%) 5 (17.9%)
Conditioning for HSCT2, n (%) TBI based BU based
20 (71.4%) 8 (28.6%)
Sex match (donor/recipient) at HSCT2, n (%) Female–female Female–male Male–male Male–female
3 (10.7%) 6 (21.4%) 14 (50.0%) 5 (17.9%)
Donor type for HSCT2, n (%) MSD Haplo-donor URD
10 (35.7%) 17 (60.7%) 1 (3.6%)
Donor change, n (%) Yes No
9 (32.1%) 19 (69.7%)
Engraftment after HSCT2 (WBC) , n (%) Yes No
27 (96.4%) 1 (3.6%)
Response to HSCT2, n (%) Complete remission Persistent leukemia
26 (92.9%) 2 (5.4%)
Acute GVHD after HSCT2, n (%) Grade 0–1 Grade 2–4
21 (75.0%) 7 (25.0%)
Chronic GVHD after HSCT2, n (%) Mild Moderate Severe No
3 (10.7%) 6 (21.4%) 2 (7.1%) 17 (60.7%)
Relapse after initial response to HSCT2, n (%) Yes No
11 (39.3%) 17 (60.7%)
Cause of death after HSCT2, n (%) Infection or other complication Relapse
7 (30.4%) 16 (69.6%)
Tab.2
Fig.3
Fig.4
Variable
Univariate analysis
OS
DFS
HR (95% CI)
P
HR (95% CI)
P
Patient-related variables Age (≤30 years vs.>30 years) Gender (female vs. male)
0.595 (0.244–1.452) 1.226 (0.412–3.653)
0.254 0.714
0.781 (0.325–1.875) 0.669 (0.225–1.982)
0.580 0.468
Disease-related variables Percentage of blasts Risk stratification pre-HSCT1 Time from HSCT1 to relapse (≤6 months vs. >6 months) Time from HSCT1 to HSCT2 (≤12 months vs. >12 months) Times from relapse to HSCT2 (≤6 months vs. >6 months)
Transplant-related variables HSCT1 Disease status pre-HSCT1 a-GVHD c-GVHD HSCT2 Donor age (≤30 years vs. >30 years) Donor sex (male vs. female) Conditioning (TBI vs. BU) for HSCT2 Donor change (yes vs. no)
Y Wang, QF Liu, LP Xu, KY Liu, XH Zhang, X Ma, ZP Fan, DP Wu, XJ Huang. Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood 2015; 125(25): 3956–3962 https://doi.org/10.1182/blood-2015-02-627786
pmid: 25940714
3
CG Kanakry, EJ Fuchs, L Luznik. Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev Clin Oncol 2016; 13(1): 10–24 https://doi.org/10.1038/nrclinonc.2015.128
pmid: 26305035
4
CH Yan, DH Liu, KY Liu, LP Xu, YR Liu, H Chen, W Han, Y Wang, YZ Qin, XJ Huang. Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood 2012; 119(14): 3256–3262 https://doi.org/10.1182/blood-2011-09-380386
pmid: 22337715
5
YJ Chang, Y Wang, XJ Huang. Haploidentical stem cell transplantation for the treatment of leukemia: current status. Expert Rev Hematol 2014; 7(5): 635–647 https://doi.org/10.1586/17474086.2014.954543
pmid: 25213459
6
B Oran, M de Lima. Prevention and treatment of acute myeloid leukemia relapse after allogeneic stem cell transplantation. Curr Opin Hematol 2011; 18(6): 388–394 https://doi.org/10.1097/MOH.0b013e32834b6158
pmid: 21897227
7
M Mielcarek, BE Storer, ME Flowers, R Storb, BM Sandmaier, PJ Martin. Outcomes among patients with recurrent high-risk hematologic malignancies after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2007; 13(10): 1160–1168 https://doi.org/10.1016/j.bbmt.2007.06.007
pmid: 17889352
8
JE Levine, T Braun, SL Penza, P Beatty, K Cornetta, R Martino, WR Drobyski, AJ Barrett, DL Porter, S Giralt, J Leis, HE Holmes, M Johnson, M Horowitz, RH Collins Jr. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. J Clin Oncol 2002; 20(2): 405–412 https://doi.org/10.1200/JCO.2002.20.2.405
pmid: 11786567
9
SJ Choi, JH Lee, JH Lee, S Kim, M Seol, YS Lee, JS Lee, WK Kim, HS Chi, KH Lee. Treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a high incidence of isolated extramedullary relapse. Leukemia 2004; 18(11): 1789–1797 https://doi.org/10.1038/sj.leu.2403523
pmid: 15385924
10
C Schmid, M Labopin, A Nagler, M Bornhäuser, J Finke, A Fassas, L Volin, G Gürman, J Maertens, P Bordigoni, E Holler, G Ehninger, E Polge, NC Gorin, HJ Kolb, V Rocha; EBMT Acute Leukemia Working Party. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol 2007; 25(31): 4938–4945 https://doi.org/10.1200/JCO.2007.11.6053
pmid: 17909197
11
M Lübbert, H Bertz, R Wäsch, R Marks, B Rüter, R Claus, J Finke. Efficacy of a 3-day, low-dose treatment with 5-azacytidine followed by donor lymphocyte infusions in older patients with acute myeloid leukemia or chronic myelomonocytic leukemia relapsed after allografting. Bone Marrow Transplant 2010; 45(4): 627–632 https://doi.org/10.1038/bmt.2009.222
pmid: 19718057
12
XJ Huang, DH Liu, KY Liu, LP Xu, H Chen, W Han. Donor lymphocyte infusion for the treatment of leukemia relapse after HLA-mismatched/haploidentical T-cell-replete hematopoietic stem cell transplantation. Haematologica 2007; 92(3): 414–417 https://doi.org/10.3324/haematol.10570
pmid: 17339194
13
M Michallet, ML Tanguy, G Socié, A Thiébaut, A Belhabri, N Milpied, J Reiffers, M Kuentz, JY Cahn, D Blaise, F Demeocq, JP Jouet, AS Michallet, N Ifrah, E Vilmer, L Molina, G Michel, B Lioure, M Cavazzana-Calvo, JL Pico, A Sadoun, D Guyotat, M Attal, H Curé, P Bordigoni, L Sutton, A Buzyn-Veil, M Tilly, N Keoirruer, N Feguex. Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Société Française de Greffe de moelle (SFGM). Br J Haematol 2000; 108(2): 400–407 https://doi.org/10.1046/j.1365-2141.2000.01851.x
pmid: 10691873
14
A Tomonari, T Iseki, J Ooi, H Nagayama, H Sato, T Takahashi, K Ito, F Nagamura, K Uchimaru, S Takahashi, N Shirafuji, A Tojo, K Tani, S Asano. Second allogeneic hematopoietic stem cell transplantation for leukemia relapse after first allogeneic transplantation: outcome of 16 patients in a single institution. Int J Hematol 2002; 75(3): 318–323 https://doi.org/10.1007/BF02982050
pmid: 11999364
15
P Tsirigotis, M Byrne, C Schmid, F Baron, F Ciceri, J Esteve, NC Gorin, S Giebel, M Mohty, BN Savani, A Nagler. Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT. Bone Marrow Transplant 2016; 51(11): 1431–1438 https://doi.org/10.1038/bmt.2016.167
pmid: 27295272
16
CH Yan, Y Wang, JZ Wang, YH Chen, Y Chen, FR Wang, YQ Sun, XD Mo, W Han, H Chen, XH Zhang, LP Xu, KY Liu, XJ Huang. Minimal residual disease- and graft-vs.-host disease-guided multiple consolidation chemotherapy and donor lymphocyte infusion prevent second acute leukemia relapse after allotransplant. J Hematol Oncol 2016; 9(1): 87 https://doi.org/10.1186/s13045-016-0319-5
pmid: 27629395
17
CH Yan, JZ Wang, DH Liu, LP Xu, H Chen, KY Liu, XJ Huang. Chemotherapy followed by modified donor lymphocyte infusion as a treatment for relapsed acute leukemia after haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion: superior outcomes compared with chemotherapy alone and an analysis of prognostic factors. Eur J Haematol 2013; 91(4): 304–314 https://doi.org/10.1111/ejh.12168
pmid: 23837640
18
T Miyamoto, T Fukuda, M Nakashima, T Henzan, S Kusakabe, N Kobayashi, J Sugita, T Mori, M Kurokawa, SI Mori. Donor lymphocyte infusion for relapsed hematological malignancies after unrelated allogeneic bone marrow transplantation facilitated by the japan marrow donor program. Biol Blood Marrow Transplant 2017; 23(6): 938–944 https://doi.org/10.1016/j.bbmt.2017.02.012
pmid: 28219836
19
T Ruutu, LC de Wreede, A van Biezen, R Brand, M Mohty, P Dreger, R Duarte, C Peters, L Garderet, S Schönland, A Gratwohl, D Niederwieser, T de Witte, N; European Society for Blood and Marrow Transplantation (EBMT) Kröger. Second allogeneic transplantation for relapse of malignant disease: retrospective analysis of outcome and predictive factors by the EBMT. Bone Marrow Transplant 2015; 50(12): 1542–1550 https://doi.org/10.1038/bmt.2015.186
pmid: 26367221
20
R Vrhovac, M Labopin, F Ciceri, J Finke, E Holler, J Tischer, B Lioure, J Gribben, L Kanz, D Blaise, P Dreger, G Held, R Arnold, A Nagler, M; Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT) Mohty. Second reduced intensity conditioning allogeneic transplant as a rescue strategy for acute leukaemia patients who relapse after an initial RIC allogeneic transplantation: analysis of risk factors and treatment outcomes. Bone Marrow Transplant 2016; 51(2): 186–193 https://doi.org/10.1038/bmt.2015.221
pmid: 26437057
21
XJ Huang, DH Liu, KY Liu, LP Xu, H Chen, W Han, YH Chen, JZ Wang, ZY Gao, YC Zhang, Q Jiang, HX Shi, DP Lu. Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies. Bone Marrow Transplant 2006; 38(4): 291–297 https://doi.org/10.1038/sj.bmt.1705445
pmid: 16883312
22
XJ Huang, DH Liu, KY Liu, LP Xu, H Chen, W Han, YH Chen, XH Zhang, DP Lu. Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation. Biol Blood Marrow Transplant 2009; 15(2): 257–265 https://doi.org/10.1016/j.bbmt.2008.11.025
pmid: 19167686
23
CH Yan, QF Liu, DP Wu, X Zhang, LP Xu, XH Zhang, Y Wang, H Huang, H Bai, F Huang, X Ma, XJ Huang. Prophylactic donor lymphocyte infusion (DLI) followed by minimal residual disease and graft-versus-host disease-guided multiple DLIs could improve outcomes after allogeneic hematopoietic stem cell transplantation in patients with refractory/relapsed acute leukemia. Biol Blood Marrow Transplant 2017; 23(8): 1311–1319 https://doi.org/10.1016/j.bbmt.2017.04.028
pmid: 28483716
24
XJ Huang, Y Wang, DH Liu, LP Xu, H Chen, YH Chen, W Han, HX Shi, KY Liu. Modified donor lymphocyte infusion (DLI) for the prophylaxis of leukemia relapse after hematopoietic stem cell transplantation in patients with advanced leukemia—feasibility and safety study. J Clin Immunol 2008; 28(4): 390–397 https://doi.org/10.1007/s10875-008-9193-4
pmid: 18347959
25
M Brüggemann, M Kotrova. Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation. Blood Adv 2017; 1(25): 2456–2466 https://doi.org/10.1182/bloodadvances.2017009845
pmid: 29296895
26
Y Wang, H Chen, J Chen, M Han, J Hu, Hu Jiong, H Huang, Y Lai, D Liu, Q Liu, T Liu, M Jiang, H Ren, Y Song, Z Sun, C Wang, J Wang, D Wu, K Xu, X Zhang, L Xu, K Liu, X Huang. The consensus on the monitoring, treatment, and prevention of leukemia relapse after allogeneic hematopoietic stem cell transplantation in China. Cancer Lett 2018; 438: 63–75 https://doi.org/10.1016/j.canlet.2018.08.030
pmid: 30217562
27
D Przepiorka, R Nath, C Ippoliti, R Mehra, F Hagemeister, K Diener, M Dimopoulos, S Giralt, I Khouri, B Samuels, et al.. A phase I–II study of high-dose thiotepa, busulfan and cyclophosphamide as a preparative regimen for autologous transplantation for malignant lymphoma. Leuk Lymphoma 1995; 17(5–6): 427–433 https://doi.org/10.3109/10428199509056853
pmid: 7549833
28
H Glucksberg, R Storb, A Fefer, CD Buckner, PE Neiman, RA Clift, KG Lerner, ED Thomas. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18(4): 295–304 https://doi.org/10.1097/00007890-197410000-00001
pmid: 4153799
29
M Eapen, SA Giralt, MM Horowitz, JP Klein, JE Wagner, MJ Zhang, MS Tallman, DI Marks, BM Camitta, RE Champlin, O Ringdén, CN Bredeson, R Martino, RP Gale, MS Cairo, MR Litzow, M deLima. Second transplant for acute and chronic leukemia relapsing after first HLA-identical sibling transplant. Bone Marrow Transplant 2004; 34(8): 721–727 https://doi.org/10.1038/sj.bmt.1704645
pmid: 15322568
30
CN Duncan, NS Majhail, R Brazauskas, Z Wang, JY Cahn, HA Frangoul, RJ Hayashi, JW Hsu, RT Kamble, KA Kasow, N Khera, HM Lazarus, AW Loren, DI Marks, RT Maziarz, P Mehta, KC Myers, M Norkin, JA Pidala, DL Porter, V Reddy, W Saber, BN Savani, HC Schouten, A Steinberg, DA Wall, AB Warwick, WA Wood, LC Yu, DA Jacobsohn, ML Sorror. Long-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes. Biol Blood Marrow Transplant 2015; 21(1): 151–158 https://doi.org/10.1016/j.bbmt.2014.10.006
pmid: 25316109
31
F Al-Qurashi, M Ayas, F Al Sharif, E Ibrahim, E Sahovic, M Al Mahr, N Chaudhri, F Al Mohareb, H Al Zahrani, A Al Jefri, H Al Omar, A Al Shanqeeti, P Seth, M Aslam, H El Solh, M Aljurf. Second allogeneic bone marrow transplantation after myeloablative conditioning analysis of 43 cases from single institution. Hematology 2004; 9(2): 123–129 https://doi.org/10.1080/10245330310001652509
pmid: 15203867
32
R Pawson, MN Potter, P Theocharous, M Lawler, M Garg, JA Yin, K Rezvani, C Craddock, S Rassam, HG Prentice. Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG± Ida) and second allogeneic stem cell transplant. Br J Haematol 2001; 115(3): 622–629 https://doi.org/10.1046/j.1365-2141.2001.03150.x
pmid: 11736947
33
BE Shaw, GJ Mufti, S Mackinnon, JD Cavenagh, RM Pearce, KE Towlson, JF Apperley, R Chakraverty, CF Craddock, MA Kazmi, TJ Littlewood, DW Milligan, A Pagliuca, KJ Thomson, DI Marks, NH Russell. Outcome of second allogeneic transplants using reduced-intensity conditioning following relapse of haematological malignancy after an initial allogeneic transplant. Bone Marrow Transplant 2008; 42(12): 783–789 https://doi.org/10.1038/bmt.2008.255
pmid: 18724393
34
AM Zeidan, PM Forde, H Symons, A Chen, BD Smith, K Pratz, H Carraway, DE Gladstone, EJ Fuchs, L Luznik, RJ Jones, J Bolaños-Meade. HLA-haploidentical donor lymphocyte infusions for patients with relapsed hematologic malignancies after related HLA-haploidentical bone marrow transplantation. Biol Blood Marrow Transplant 2014; 20(3): 314–318 https://doi.org/10.1016/j.bbmt.2013.11.020
pmid: 24296490
35
SR Goldsmith, M Slade, JF DiPersio, P Westervelt, MA Schroeder, F Gao, R Romee. Donor-lymphocyte infusion following haploidentical hematopoietic cell transplantation with peripheral blood stem cell grafts and PTCy. Bone Marrow Transplant 2017; 52(12): 1623–1628 https://doi.org/10.1038/bmt.2017.193
pmid: 29035393
36
N Bejanyan, DJ Weisdorf, BR Logan, HL Wang, SM Devine, M de Lima, DW Bunjes, MJ Zhang. Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: a center for international blood and marrow transplant research study. Biol Blood Marrow Transplant 2015; 21(3): 454–459 https://doi.org/10.1016/j.bbmt.2014.11.007
pmid: 25460355
37
M Christopeit, O Kuss, J Finke, U Bacher, DW Beelen, M Bornhäuser, R Schwerdtfeger, WA Bethge, N Basara, M Gramatzki, J Tischer, HJ Kolb, L Uharek, RG Meyer, D Bunjes, C Scheid, H Martin, D Niederwieser, N Kröger, H Bertz, H Schrezenmeier, C Schmid. Second allograft for hematologic relapse of acute leukemia after first allogeneic stem-cell transplantation from related and unrelated donors: the role of donor change. J Clin Oncol 2013; 31(26): 3259–3271 https://doi.org/10.1200/JCO.2012.44.7961
pmid: 23918951
38
K Horstmann, A Boumendil, J Finke, H Finel, E Kanfer, G Milone, N Russell, A Bacigalupo, Y Chalandon, JL Diez-Martin, N Ifrah, MJ Chacon, P Dreger. Second allo-SCT in patients with lymphoma relapse after a first allogeneic transplantation. A retrospective study of the EBMT Lymphoma Working Party. Bone Marrow Transplant 2015; 50(6): 790–794 https://doi.org/10.1038/bmt.2015.12
pmid: 25751644
39
S Meshinchi, WM Leisenring, PA Carpenter, AE Woolfrey, EL Sievers, JP Radich, JE Sanders. Survival after second hematopoietic stem cell transplantation for recurrent pediatric acute myeloid leukemia. Biol Blood Marrow Transplant 2003; 9(11): 706–713 https://doi.org/10.1016/j.bbmt.2003.08.003
pmid: 14652854
40
A Bosi, D Laszlo, M Labopin, J Reffeirs, M Michallet, E Gluckman, PE Alessandrino, F Locatelli, JP Vernant, J Sierra, JP Jouet, F; Acute Leukemia Working Party of the European Blood and Marrow Transplant Group Frassoni. Second allogeneic bone marrow transplantation in acute leukemia: results of a survey by the European Cooperative Group for Blood and Marrow Transplantation. J Clin Oncol 2001; 19(16): 3675–3684 https://doi.org/10.1200/JCO.2001.19.16.3675
pmid: 11504749
41
F Keil, E Prinz, P Kalhs, K Lechner, K Moser, I Schwarzinger, U Jäger, C Fonatsch, N Worel, C Mannhalter, W Rabitsch, H Loidolt, A Schulenburg, M Mitterbauer, P Höcker, HT Greinix. Treatment of leukemic relapse after allogeneic stem cell transplantation with cytotoreductive chemotherapy and/or immunotherapy or second transplants. Leukemia 2001; 15(3): 355–361 https://doi.org/10.1038/sj.leu.2402048
pmid: 11237057
42
IW Blau, N Basara, M Bischoff, S Günzelmann, E Römer, D Kirsten, B Schmetzer, MG Kiehl, AA Fauser. Second allogeneic hematopoietic stem cell transplantation as treatment for leukemia relapsing following a first transplant. Bone Marrow Transplant 2000; 25(1): 41–45 https://doi.org/10.1038/sj.bmt.1702101
pmid: 10654013
43
JP Radich, JE Sanders, CD Buckner, PJ Martin, FB Petersen, W Bensinger, GB McDonald, M Mori, G Schoch, JA Hansen. Second allogeneic marrow transplantation for patients with recurrent leukemia after initial transplant with total-body irradiation-containing regimens. J Clin Oncol 1993; 11(2): 304–313 https://doi.org/10.1200/JCO.1993.11.2.304
pmid: 8426208
44
ML Arellano, A Langston, E Winton, CR Flowers, EK Waller. Treatment of relapsed acute leukemia after allogeneic transplantation: a single center experience. Biol Blood Marrow Transplant 2007; 13(1): 116–123 https://doi.org/10.1016/j.bbmt.2006.09.005
pmid: 17222760
45
A Muñoz, I Badell, T Olivé, A Verdeguer, P Gómez, E; BureoSpanish Working Party for Bone Marrow Transplantation in Children (GETMON). Second allogeneic hematopoietic stem cell transplantation in hematologic malignancies in children: long-term results of a multicenter study of the Spanish Working Party for Bone Marrow Transplantation in Children (GETMON). Haematologica 2002; 87(3): 331–332
pmid: 11869952
46
M Kato, Y Horikoshi, Y Okamoto, Y Takahashi, D Hasegawa, K Koh, J Takita, M Inoue, H Kigasawa, A Ogawa, Y Sasahara, K Kawa, H Yabe, H Sakamaki, R Suzuki, K Kato. Second allogeneic hematopoietic SCT for relapsed ALL in children. Bone Marrow Transplant 2012; 47(10): 1307–1311 https://doi.org/10.1038/bmt.2012.29
pmid: 22367344
47
ZA McIver, F Yin, T Hughes, M Battiwalla, S Ito, E Koklanaris, J Haggerty, NF Hensel, AJ Barrett. Second hematopoietic SCT for leukemia relapsing after myeloablative T cell-depleted transplants does not prolong survival. Bone Marrow Transplant 2013; 48(9): 1192–1197 https://doi.org/10.1038/bmt.2013.39
pmid: 23524640
48
S Naik, C Martinez, K Leung, G Sasa, NY Nguyen, MF Wu, S Gottschalk, M Brenner, H Heslop, R Krance. Outcomes after second hematopoietic stem cell transplantations in pediatric patients with relapsed hematological malignancies. Biol Blood Marrow Transplant 2015; 21(7): 1266–1272 https://doi.org/10.1016/j.bbmt.2015.02.024
pmid: 25765555
49
HW Chueh, SH Lee, KW Sung, KH Yoo, HH Koo. Second allogeneic stem cell transplantation in hematologic malignancies: a single-center experience. J Pediatr Hematol Oncol 2013; 35(6): 424–429 https://doi.org/10.1097/MPH.0b013e31829b7f58
pmid: 23887021
50
L Castagna, B Sarina, S Bramanti, P Perseghin, J Mariotti, L Morabito. Donor lymphocyte infusion after allogeneic stem cell transplantation. Transfus Apheresis Sci 2016; 54(3): 345–355 https://doi.org/10.1016/j.transci.2016.05.011
pmid: 27216544
51
A Spyridonidis, M Labopin, C Schmid, L Volin, I Yakoub-Agha, M Stadler, N Milpied, G Socie, P Browne, S Lenhoff, MA Sanz, M Aljurf, M Mohty, V Rocha; Immunotherapy Subcommittee of Acute Leukemia Working Party. Outcomes and prognostic factors of adults with acute lymphoblastic leukemia who relapse after allogeneic hematopoietic cell transplantation. An analysis on behalf of the Acute Leukemia Working Party of EBMT. Leukemia 2012; 26(6): 1211–1217 https://doi.org/10.1038/leu.2011.351
pmid: 22290066
52
RE Brouwer, P van der Heiden, GM Schreuder, A Mulder, G Datema, JD Anholts, R Willemze, FH Claas, JH Falkenburg. Loss or downregulation of HLA class I expression at the allelic level in acute leukemia is infrequent but functionally relevant, and can be restored by interferon. Hum Immunol 2002; 63(3): 200–210 https://doi.org/10.1016/S0198-8859(01)00381-0
pmid: 11872238
53
SJ Choi, JH Lee, JH Lee, S Kim, YS Lee, M Seol, SG Ryu, JS Lee, WK Kim, S Jang, CJ Park, HS Chi, KH Lee. Treatment of relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a prospective study. Bone Marrow Transplant 2005; 36(2): 163–169 https://doi.org/10.1038/sj.bmt.1705024
pmid: 15937507
54
A Deol, LG Lum. Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited. Cancer Treat Rev 2010; 36(7): 528–538 https://doi.org/10.1016/j.ctrv.2010.03.004
pmid: 20381970
55
C Hosing, RM Saliba, M Shahjahan, EH Estey, D Couriel, S Giralt, B Andersson, RE Champlin, M De Lima. Disease burden may identify patients more likely to benefit from second allogeneic hematopoietic stem cell transplantation to treat relapsed acute myelogenous leukemia. Bone Marrow Transplant 2005; 36(2): 157–162 https://doi.org/10.1038/sj.bmt.1705011
pmid: 15937511
56
PH Imus, AL Blackford, M Bettinotti, B Iglehart, A Dietrich, N Tucker, H Symons, KR Cooke, L Luznik, EJ Fuchs, RA Brodsky, WH Matsui, CA Huff, D Gladstone, RF Ambinder, IM Borrello, LJ Swinnen, RJ Jones, J Bolaños-Meade. Major histocompatibility mismatch and donor choice for second allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 2017; 23(11): 1887–1894 https://doi.org/10.1016/j.bbmt.2017.07.014
pmid: 28754545
57
C Schmid, M Schleuning, G Ledderose, J Tischer, HJ Kolb. Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 2005; 23(24): 5675–5687 https://doi.org/10.1200/JCO.2005.07.061
pmid: 16110027
58
C Schmid, M Schleuning, R Schwerdtfeger, B Hertenstein, E Mischak-Weissinger, D Bunjes, SV Harsdorf, C Scheid, U Holtick, H Greinix, F Keil, B Schneider, M Sandherr, G Bug, J Tischer, G Ledderose, M Hallek, W Hiddemann, HJ Kolb. Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood 2006; 108(3): 1092–1099 https://doi.org/10.1182/blood-2005-10-4165
pmid: 16551971
59
F Saraceni, M Labopin, A Brecht, N Kröger, M Eder, J Tischer, H Labussière-Wallet, H Einsele, D Beelen, D Bunjes, D Niederwieser, T Bochtler, BN Savani, M Mohty, A Nagler. Fludarabine-treosulfan compared to thiotepa-busulfan-fludarabine or FLAMSA as conditioning regimen for patients with primary refractory or relapsed acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). J Hematol Oncol 2019; 12(1): 44 https://doi.org/10.1186/s13045-019-0727-4
pmid: 31023346
60
R Ram, C Scheid, O Amit, JM Chemnitz, Y Moshe, M Hallek, D Wolf, I Avivi, U Holtick. Sequential therapy for patients with primary refractory acute myeloid leukemia: a historical prospective analysis of the German and Israeli experience. Haematologica 2019; 104(9): 1798–1803 https://doi.org/10.3324/haematol.2018.203869
pmid: 30733263
61
N Kono, K Ohashi, E Sasaki, Y Okoshi, D Mizuchi, S Mori, H Akiyama, K Karasawa, H Kaku, R Okamoto, Y Maeda, T Sasaki, Y Okuyama, K Hiruma, H Sakamaki. Second allogeneic peripheral blood stem cell transplantation with fludarabine-based low-intensity conditioning regimen for relapsed myelodysplastic syndrome after allogeneic bone marrow transplantation. Int J Hematol 2001; 73(1): 122–125 https://doi.org/10.1007/BF02981914
pmid: 11372748
62
C Grüllich, H Bertz, A Spyridonidis, CI Müller, J Finke. A fludarabine, thiotepa reduced toxicity conditioning regimen designed specifically for allogeneic second haematopoietic cell transplantation after failure of previous autologous or allogeneic transplantation. Bone Marrow Transplant 2008; 41(10): 845–850 https://doi.org/10.1038/sj.bmt.1705989
pmid: 18209719
63
K Kishi, S Takahashi, H Gondo, S Shiobara, A Kanamaru, S Kato, N Hirabayashi, Y Moriyama, M Harada, S Asano, H Hara, A Shibata. Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes. Bone Marrow Transplant 1997; 19(5): 461–466 https://doi.org/10.1038/sj.bmt.1700680
pmid: 9052912
