B-cell lymphoma comprises the majority of non-Hodgkin lymphomas worldwide. Hematopoietic cell transplantation (HCT) is used for patients with high-risk, relapsed, or refractory B-cell lymphoma.
Methods
The current medical literature and the results of recently published trials were reviewed to provide an update on the most common indications for HCT in B-cell lymphoma.
Results
Autologous HCT has evolving and new roles in the treatment of patients with high-risk diffuse large B-cell cell lymphoma, mantle cell lymphoma, and HIV-related lymphoma. Reduced-intensity conditioning has largely replaced older myeloablative conditioning regimens, making allogeneic transplantation safer for more patients with lymphoma.
Conclusions
The indication and timing of HCT depend on the patient's histology, age, and response to previous therapies. HCT is an essential component in the armamentarium to treat B-cell lymphoma.
References
1.
SiegelS., WardE., BrawleyO.. Cancer statistics, 2011.CA Cancer J Clin.2011; 61: 212–236.
2.
BuddeL.E., GuthrieK.A., TillB.G.. Mantle cell lymphoma international prognostic index but not pretransplantation induction regimen predicts survival for patients with mantle-cell lymphoma receiving highdose therapy and autologous stem-cell transplantation.J Clin Oncol.2011; 29(22): 3023–3029.
3.
AyalaE., TomblynM.. Hematopoietic cell transplantation for lymphomas.Cancer Control.2011; 18(4): 246–257.
4.
OlianskyD.M., CzuczmanM., FisherR.I.. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of diffuse large B-cell lymphoma: update of the 2001 evidence-based review.Biol Blood Marrow Transplant.2011; 17(1): 20–47 e30.
5.
StiffP.J., UngerJ.M., CookJ.. Randomized phase III US/Canadian intergroup trial (SWOG S9704) comparing CHOP ± R for eight cycles to CHOP ± R for six cycles followed by autotransplant for patients with high-intermediate (H-Int) or high IPI grade diffuse aggressive non-Hodgkin lymphoma (NHL).J Clin Oncol.2011; 29(suppl): 8001. Abstract.
6.
PhilipT., GuglielmiC., HagenbeekA.. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma.N Engl J Med.1995; 333(23): 1540–1545.
7.
JantunenE., CanalsC., RambaldiA.. Autologous stem cell transplantation in elderly patients (> or = 60 years) with diffuse large B-cell lymphoma: an analysis based on data in the European Blood and Marrow Transplantation registry.Haematologica.2008; 93(12): 1837–1842.
8.
BuadiF.K., MicallefI.N., AnsellS.M.. Autologous hematopoietic stem cell transplantation for older patients with relapsed non-Hodgkin's lymphoma.Bone Marrow Transplant.2006; 37(11): 1017–1022.
9.
JantunenE., ItalaM., JuvonenE.. Autologous stem cell transplantation in elderly (>60 years) patients with non-Hodgkin's lymphoma: a nation-wide analysis.Bone Marrow Transplant.2006; 37(4): 367–372.
10.
LazarusH.M., CarrerasJ., BoudreauC.. Influence of age and histology on outcome in adult non-Hodgkin lymphoma patients undergoing autologous hematopoietic cell transplantation (HCT): a report from the Center For International Blood & Marrow Transplant Research (CIBMTR).Biol Blood Marrow Transplant.2008; 14(12): 1323–1333.
11.
CoiffierB., LepageE., BriereJ.. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma.N Engl J Med.2002; 346(4): 235–242.
12.
FeugierP., Van HoofA., SebbanC.. Long-term results of the RCHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte.J Clin Oncol.2005; 23(18): 4117–4126.
13.
PfreundschuhM., TrumperL., OsterborgA.. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group.Lancet Oncol.2006; 7(5): 379–391.
14.
HorwitzS.M., NegrinR.S., BlumeK.G.. Rituximab as adjuvant to highdose therapy and autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma.Blood.2004; 103(3): 777–783.
15.
KewalramaniT., ZelenetzA.D., NimerS.D.. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma.Blood.2004; 103(10): 3684–3688.
16.
FlinnI.W., O'DonnellP.V., GoodrichA.. Immunotherapy with rituximab during peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.Biol Blood Marrow Transplant.2000; 6(6): 628–632.
17.
BenekliM., HahnT., ShafiF.. Effect of rituximab on peripheral blood stem cell mobilization and engraftment kinetics in non-Hodgkin's lymphoma patients.Bone Marrow Transplant.2003; 32(2): 139–143.
18.
VellengaE., van PuttenW.L., van ‘t VeerM.B.. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial.Blood.2008; 111(2): 537–543.
19.
FenskeT.S., HariP.N., CarrerasJ.. Impact of pre-transplant rituximab on survival after autologous hematopoietic stem cell transplantation for diffuse large B-cell lymphoma.Biol Blood Marrow Transplant.2009; 15(11): 1455–1464.
20.
TarellaC., ZanniM., MagniM.. Rituximab improves the efficacy of highdose chemotherapy with autograft for high-risk follicular and diffuse large B-cell lymphoma: a multicenter Gruppo Italiano Terapie Innovative nei Linfomi survey.J Clin Oncol.2008; 26(19): 3166–3175.
21.
Le GouillS., KrögerN., DhedinN.. Reduced-intensity conditioning allogeneic stem cell transplantation for relapsed/refractory mantle cell lymphoma: a multicenter experience.Ann Oncol.2012 Mar 22. Epub ahead of print.
22.
KhouriI.F., Saliba, RimaM.. Efficacy and safety of yttrium 90 (90Y) ibritumomab tiuxetan in autologous and nonmyeloablative stem cell transplantation (NST) for relapsed non-Hodgkin's lymphoma (NHL).Blood (ASH Annual Meeting Abstracts).2006; 108. Abstract 315.
23.
ShimoniA., ZwasS.T., OksmanY.. Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with highdose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin's lymphoma.Exp Hematol.2007; 35(4): 534–540.
24.
KrishnanA., NademaneeA., FungH.C.. Phase II trial of a transplantation regimen of yttrium-90 ibritumomab tiuxetan and highdose chemotherapy in patients with non-Hodgkin's lymphoma.J Clin Oncol.2008; 26(1): 90–95.
25.
Shimabukuro-VornhagenA., HübelK., ScheidC.. Yttrium-90 ibritumomab tiuxetan combined with highdose BEAM chemotherapy and autologous stem cell transplantation for relapsed/refractory B-cell non-Hodgkin's lymphoma.J Clin Oncol.2008; 26(15 suppl). Abstract 8615.
26.
DecaudinD., MounierN., TillyH.. (90)Y ibritumomab tiuxetan (Zevalin) combined with BEAM (Z -BEAM) conditioning regimen plus autologous stem cell transplantation in relapsed or refractory low-grade CD20-positive B-cell lymphoma: a GELA phase II prospective study.Clin Lymphoma Myeloma Leuk.2011; 11(2): 212–218.
27.
VoseJ.M., BiermanP.J., EnkeC.. Phase I trial of iodine-131 tositumomab with highdose chemotherapy and autologous stem-cell transplantation for relapsed non-Hodgkin's lymphoma.J Clin Oncol.2005; 23(3): 461–467.
28.
VoseJ., BociekG., LoberizaF.. Radioimmunotherapy with 131-I tositumomab enhanced survival in good prognosis relapsed and highrisk diffuse large B-cell lymphoma (DLBCL) patients receiving highdose chemotherapy and autologous stem cell transplantation.J Clin Oncol.2007; 25(18 suppl). Abstract 8013.
29.
NademaneeA., FormanS., MolinaA.. A phase 1/2 trial of highdose yttrium-90-ibritumomab tiuxetan in combination with highdose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma.Blood.2005; 106(8): 2896–2902.
30.
WinterJ.N., InwardsD.J., SpiesS.. Yttrium-90 ibritumomab tiuxetan doses calculated to deliver up to 15 Gy to critical organs may be safely combined with highdose BEAM and autologous transplantation in relapsed or refractory B-cell non-Hodgkin's lymphoma.J Clin Oncol.2009; 27(10): 1653–1659.
31.
PressO.W., EaryJ.F., GooleyT.. A phase I/II trial of iodine-131-tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed B-cell lymphomas.Blood.2000; 96(9): 2934–2942.
32.
VoseJ.M., CarterS.L., BurnsL.J.. Randomized phase III trial of 131iodine-tositumomab (Bexxar)/carmustine, etoposide, cytarabine, melphalan (BEAM) vs rituximab/BEAM and autologous stem cell transplantation for relapsed diffuse large B-cell lymphoma (DLBCL): no difference in progression-free (PFS) or overall survival (OS). 53rd ASH Annual Meeting and Exposition, December 10-13, 2011, San Diego, CA. Abstract 661. http://ash.confex.com/ash/2011/webprogram/Paper39888.html. Accessed April 5, 2012.
33.
LazarusH.M., ZhangM.J., CarrerasJ.. A comparison of HLA-identical sibling allogeneic versus autologous transplantation for diffuse large B-cell lymphoma: a report the CIBMTR.Biol Blood Marrow Transplant.2010; 16(1): 35–45.
34.
SirventA., DhedinN., MichalletM.. Low nonrelapse mortality and prolonged long-term survival after reduced-intensity allogeneic stem cell transplantation for relapsed or refractory diffuse large B-cell lymphoma: report of the Société Française de Greffe de Moelle et de Thérapie Cellulaire.Biol Blood Marrow Transplant.2010; 16(1): 78–85.
35.
BacherU., KlyuchnikovE., CarrerasJ.. Conditioning intensity in allogeneic hematopoietic cell transplantation (alloHCT) for diffuse large B-cell lymphoma (DLBCL).Blood (ASH Annual Meeting Abstracts).2011; 118. Abstract 501.
36.
FigueroaJ., PerkinsJ., AnasettiC.. Myeloablative doses of busulfan and fludarabine as conditioning for allogeneic stem cell transplantation in non-Hodgkin's lymphoma.Biol Blood Marrow Transplant.2012; 18(suppl 2): S297.
37.
van KampenR.J., CanalsC., SchoutenH.C.. Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-Hodgkin's lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European Group for Blood and Marrow Transplantation Registry.J Clin Oncol.2011; 29(10): 1342–1348.
SebbanC., MounierN., BrousseN.. Standard chemotherapy with interferon compared with CHOP followed by highdose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA).Blood.2006; 108(8): 2540–2544.
40.
LenzG., DreylingM., SchiegnitzE.. Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group.Blood.2004; 104(9): 2667–2674.
41.
LadettoM., De MarcoF., BenedettiF.. Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage.Blood.2008; 111(8): 4004–4013.
42.
GyanE., FoussardC., BertrandP.. Highdose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years.Blood.2009; 113(5): 995–1001.
43.
SchoutenH.C., QianW., KvaloyS.. Highdose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial.J Clin Oncol.2003; 21(21): 3918–3927.
44.
van BesienK., LoberizaF.R.Jr, BajorunaiteR.. Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma.Blood.2003; 102(10): 3521–3529.
45.
PeniketA.J., Ruiz de ElviraM.C., TaghipourG.. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation.Bone Marrow Transplant.2003; 31(8): 667–678.
46.
HariP., CarrerasJ., ZhangM.J.. Allogeneic transplants in follicular lymphoma: higher risk of disease progression after reduced-intensity compared to myeloablative conditioning.Biol Blood Marrow Transplant.2008; 14(2): 236–245.
47.
SheaT., JohnsonJ., WesterveltP.. Reduced-intensity allogeneic transplantation provides high event-free and overall survival in patients with advanced indolent B-cell malignancies: CALGB 109901.Biol Blood Marrow Transplant.2011; 17(9): 1395–1403.
48.
ThomsonK.J., MorrisE.C., MilliganD.. T-cell-depleted reducedintensity transplantation followed by donor leukocyte infusions to promote graft-versus-lymphoma activity results in excellent long-term survival in patients with multiply relapsed follicular lymphoma.J Clin Oncol.2010; 28(23): 3695–3700.
49.
PinanaJ.L., MartinoR., GayosoJ.. Reduced intensity conditioning HLA identical sibling donor allogeneic stem cell transplantation for patients with follicular lymphoma: long-term follow-up from two prospective multicenter trials.Haematologica.2010; 95(7): 1176–1182.
50.
RezvaniA.R., StorerB., MarisM.. Nonmyeloablative allogeneic hematopoietic cell transplantation in relapsed, refractory, and transformed indolent non-Hodgkin's lymphoma.J Clin Oncol.2008; 26(2): 211–217.
51.
KhouriI.F., McLaughlinP., SalibaR.M.. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab.Blood.2008; 111(12): 5530–5536.
52.
TomblynM.R., EwellM., BredesonC.. Autologous versus reduced-intensity allogeneic hematopoietic cell transplantation for patients with chemosensitive follicular non-Hodgkin lymphoma beyond first complete response or first partial response.Biol Blood Marrow Transplant.2011; 17(7): 1051–1057.
53.
AviviI., MontotoS., CanalsC.. Matched unrelated donor stem cell transplant in 131 patients with follicular lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.Br J Haematol.2009; 147(5): 719–728.
54.
GhielminiM., ZuccaE.. How I treat mantle cell lymphoma.Blood.2009; 114(8): 1469–1476.
55.
RomagueraJ.E., FayadL.E., FengL.. Ten-year follow-up after intense chemoimmunotherapy with Rituximab-HyperCVAD alternating with Rituximab-high dose methotrexate/cytarabine (R-MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma.Br J Haematol.2010; 150(2): 200–208.
56.
KettererN., SallesG., EspinouseD.. Intensive therapy with peripheral stem cell transplantation in 16 patients with mantle cell lymphoma.Ann Oncol.1997; 8(7): 701–704.
57.
StewartD.A., VoseJ.M., WeisenburgerD.D.. The role of highdose therapy and autologous hematopoietic stem cell transplantation for mantle cell lymphoma.Ann Oncol.1995; 6(3): 263–266.
58.
MilpiedN., GaillardF., MoreauP.. Highdose therapy with stem cell transplantation for mantle cell lymphoma: results and prognostic factors, a single center experience.Bone Marrow Transplant.1998; 22(7): 645–650.
59.
VandenbergheE., Ruiz de ElviraC., LoberizaF.R.. Outcome of autologous transplantation for mantle cell lymphoma: a study by the European Blood and Bone Marrow Transplant and Autologous Blood and Marrow Transplant Registries.Br J Haematol.2003; 120(5): 793–800.
60.
DreylingM., LenzG., HosterE.. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network.Blood.2005; 105(7): 2677–2684.
61.
MangelJ., LeitchH.A., ConnorsJ.M.. Intensive chemotherapy and autologous stem-cell transplantation plus rituximab is superior to conventional chemotherapy for newly diagnosed advanced stage mantle-cell lymphoma: a matched pair analysis.Ann Oncol.2004; 15(2): 283–290.
62.
RitchieD.S., SeymourJ.F., GriggA.P.. The hyper-CVAD-rituximab chemotherapy programme followed by highdose busulfan, melphalan and autologous stem cell transplantation produces excellent event-free survival in patients with previously untreated mantle cell lymphoma.Ann Hematol.2007; 86(2): 101–105.
63.
VoseJ., LoberizaF., BiermanP.. Mantle cell lymphoma (MCL): induction therapy with HyperCVAD/Highdose methotrexate and cytarabine (M-C) (± rituximab) improves results of autologous stem cell transplant in first remission.J Clin Oncol 2006 ASCO Ann Meet Proc. Part I.2006; 24(18s June 20 suppl);2006. Abstract 7511.
64.
GeislerC.H., KolstadA., LaurellA.. Long-term progression-free survival of mantle cell lymphoma after intensive frontline immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group.Blood.2008; 112(7): 2687–2693.
65.
AndersenN.S., PedersenL., ElonenE.. Primary treatment with autologous stem cell transplantation in mantle cell lymphoma: outcome related to remission pretransplant.Eur J Haematol.2003; 71: 73–80.
66.
GeislerC.H., KolstadA., LaurellA.. The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the International Prognostic Index (IPI) in predicting survival following intensive first-line immunochemotherapy and autologous stem cell transplantation (ASCT).Blood.2010; 115(8): 1530–1533.
67.
DamonL.E., JohnsonJ.L., NiedzwieckiD.. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantlecell lymphoma: CALGB 59909.J Clin Oncol.2009; 27(36): 6101–6108.
68.
TamC.S., BassettR., LedesmaC.. Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma.Blood.2009; 113(18): 4144–4152.
69.
LacasceA.S., VandergriftJ.L., RodriguezM.A.. Comparative outcome of initial therapy for younger patients with mantle cell lymphoma: an analysis from the NCCN NHL Database.Blood.2012; 119(9): 2093–2099.
70.
JantunenE., CanalsC., AttalM.. Autologous stem-cell transplantation in patients with mantle cell lymphoma beyond 65 years of age: a study from the European Group for Blood and Marrow Transplantation (EBMT).Ann Oncol.2012; 23(1): 166–171.
71.
LaudiN., AroraM., BurnsL.. Efficacy of highdose therapy and hematopoietic stem cell transplantation for mantle cell lymphoma.Am J Hematol.2006; 81(7): 519–524.
72.
KrogerN., HoffknechtM., DregerP.. Long-term disease-free survival of patients with advanced mantle-cell lymphoma following highdose chemotherapy.Bone Marrow Transplant.1998; 21(1): 55–57.
73.
MarisM.B., SandmaierB.M., StorerB.E.. Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma.Blood.2004; 104(12): 3535–3542.
74.
CookG., SmithG.M., KirklandK.. Outcome following reducedintensity allogeneic stem cell transplantation (RIC AlloSCT) for relapsed and refractory mantle cell lymphoma (MCL): a study of the British Society for Blood and Marrow Transplantation.Biol Blood Marrow Transplant.2010; 16(10): 1419–1427.
75.
FenskeT.S., CarrerasJ., ZhangM.. Outcome of patients with mantle cell lymphoma undergoing autologous versus reduced-intensity allogeneic transplantation.Ann Oncol.2011; 22(suppl 4): iv87.
76.
EngelsE.A., BiggarR.J., HallH.I.. Cancer risk in people infected with human immunodeficiency virus in the United States.Int J Cancer.2008; 123(1): 187–194.
77.
LimS.T., KarimR., NathwaniB.N.. AIDS-related Burkitt's lymphoma versus diffuse large-cell lymphoma in the pre-highly active antiretroviral therapy (HAART) and HAART eras: significant differences in survival with standard chemotherapy.J Clin Oncol.2005; 23(19): 4430–4438.
78.
KrishnanA., MolinaA., ZaiaJ.. Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas.Blood.2005; 105(2): 874–878.
79.
SpitzerT.R., AmbinderR.F., LeeJ.Y.. Dose-reduced busulfan, cyclophosphamide, and autologous stem cell transplantation for human immunodeficiency virus-associated lymphoma: AIDS Malignancy Consortium study 020.Biol Blood Marrow Transplant.2008; 14(1): 59–66.
80.
BalsalobreP., Diez-MartinJ.L., ReA.. Autologous stem-cell transplantation in patients with HIV-related lymphoma.J Clin Oncol.2009; 27(13): 2192–2198.
81.
Diez-MartinJ.L., BalsalobreP., ReA.. Comparable survival between HIV+ and HIV- non-Hodgkin and Hodgkin lymphoma patients undergoing autologous peripheral blood stem cell transplantation.Blood.2009; 113(23): 6011–6014.
82.
KrishnanA., PalmerJ.M., ZaiaJ.A.. HIV status does not affect the outcome of autologous stem cell transplantation (ASCT) for non-Hodgkin lymphoma (NHL).Biol Blood Marrow Transplant.2010; 16(9): 1302–1308.
HuzickaI.. Could bone marrow transplantation cure AIDS?Med Hypotheses.1999; 52(3): 247–257.
85.
GuptaV., TomblynM., PedersenT.L.. Allogeneic hematopoietic cell transplantation in human immunodeficiency virus-positive patients with hematologic disorders: a report from the center for international blood and marrow transplant research.Biol Blood Marrow Transplant.2009; 15(7): 864–871.
