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Total Marrow Irradiation and Total Lymphoid Irradiation in Lymphoma and Advanced Hematologic Malignancies: The Genoa Experience

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Total Marrow Irradiation

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Abstract

Currently, the choice of conditioning regimen is based on the use of the least-toxic regimen to achieve the optimal therapeutic result. Total marrow irradiation (TMI) may be an attractive method to target specific body structures like those with leukemia burden, without the risk of severe radiation-induced side effects. We like to report the clinical and technical experience grew up in Genoa during the last 10 years. The pioneer study was to investigate the feasibility of delivery TMI as “selective boost” modality to increase the radiation dose to the marrow after a conventional 12 Gy TBI. The capability of high radiation dose conformity around the selected bones, added to the high sensitivity proven to radiation in multiple myeloma, stimulated the investigation on the feasibility of a hypofractionated schedule (4 Gy × 3 consecutive daily fractions) during the autologous stem cell transplantation. The ability to modulate and paint the radiation dose around extended targets makes Helical Tomotherapy (HT) a potential support also in advanced lymphoma. Classical total lymphoid irradiation (TLI), used at the beginning of the 1980s, can now be revival and also investigated in the setting of reduced-intensity conditioning regimen both in autologous and allogeneic transplantation.

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References

  1. Thomas ED, Buckner CD, Banaji M, Clift RA, Fefer A, Flournoy N, Goodell BW, Hickman RO, Lerner KG, Neiman PE, Sale GE, Sanders JE, Singer J, Stevens M, Storb R, Weiden PL. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. sl. Blood. 1977;49(4):511–33.

    Article  CAS  PubMed  Google Scholar 

  2. Barrett AJ, Kendra JR, Lucas CF, Joss DV, Joshi R, Desai M, Jones KH, Phillips RH, Rogers TR, Tabara Z, Williamson S, Hobbs JR. Bone marrow transplantation for acute lymphoblastic leukemia. Br J Haematol. 1982;52:181–8.

    Article  CAS  PubMed  Google Scholar 

  3. Bortin MM, Rimm AA. Interstitial pneumonitis: dose rate vs total dose of radiation. Int J Radiat Oncol Biol Phys. 1982;8:1815.

    Article  CAS  PubMed  Google Scholar 

  4. Thomas ED, Storb R. Bone marrow transplantation for acute myelogenous leukemia. Lancet. 1982;320:1408.

    Article  Google Scholar 

  5. Shank B. Techniques of magna-field irradiation. Int J Radiat Oncol Biol Phys. 1983;9:1925.

    Article  CAS  PubMed  Google Scholar 

  6. Viatle V, Bacigalupo A, Van Lint MT, Frassoni G, Ricci G, Siracusa G, Marziano G, Vitali ML, Scielzo G, Tomassini A, Bistolfi F, Marmont M. Fractionated total body irradiation in marrow transplantation for leukemia. Br J Hematol. 1983;55:547–54.

    Article  Google Scholar 

  7. Scarpati D, Corvò R, Frassoni F, Guenzi M, Carella AM, Santini G, Vitale V, Franzone P. Total body irradiation before allogeneic and autologous bone marrow transplantation: a ten year Genoa experience. Radiother Oncol. 1990;18:135–8.

    Article  PubMed  Google Scholar 

  8. Frassoni F, Scarpati D, Bacigalupo A, Vitale V, Corvo R, Miceli S, Gualandi F, Occhini D, Clavio M, van Lint MT, Marmont A. The effect of total body irradiation dose and chronic graft-versus-host disease on leukemic relapse after allogeneic bone marrow transplantation. Br J Haematol. 1989;73:211–6.

    Article  CAS  PubMed  Google Scholar 

  9. Scarpati D, Frassoni F, Vitale V, Corvò R, Franzone P, Barra S, Guenzi M, Orsatti M. Total body irradiation in acute myeloid leukemia and chronic myelogenous leukemia: influence of dose and dose-rate on leukemia relapse. Int J Radiat Oncol Biol Phys. 1989;17:547–52.

    Article  CAS  PubMed  Google Scholar 

  10. Apperley JF, Jones L, Hale G, Waldmann H, Hows J, Rombos Y, Tsatalas C, Marcus RE, Goolden. Bone marrow transplantation for patients with chronic myeloid leukaemia: T-cell depletion with Campath-1 reduces the incidence of graft-versus-host disease but may increase the risk of leukaemic relapse. Bone Marrow Transplant. 1986;1:53–66.

    CAS  PubMed  Google Scholar 

  11. Bacigalupo A, Vitale V, Corvò R, Barra S, Lamparelli T, Gualandi F, Mordini N, Berisso G, Bregante S, Raiola AM, Van Lint MT, Frassoni F. The combined effect of total body irradiation (TBI) and cyclosporin A (Cy A) on the risk of relapse in patients with acute myeloid leukemia undergoing allogeneic bone marrow transplantation. Br J Hematol. 2000;108:99–104.

    Article  CAS  Google Scholar 

  12. Corvò R, Lamparelli T, Bruno B, Barra S, Van Lint MT, Vitale V, Bacigalupo A. Low dose fractionated total body irradiation (TBI) adversely affects prognosis of patients with leukemia receiving an HLA-matched allogeneic bone marrow transplant from an unrelated donor (UD-BMT). Bone Marrow Transplant. 2002;30:717–23.

    Article  PubMed  Google Scholar 

  13. Passweg JR, Baldomero H, Basak GW, Chabannon C, Corbacioglu S, Duarte R, Kuball J, Lankester A, Montoto S, de Latour RP, Snowden JA, Styczynski J, Yakoub-Agha I, Arat M, Mohty M, Kröger N; European Society for Blood and Marrow Transplantation (EBMT). The EBMT activity survey report 2017: a focus on allogeneic HCT for nonmalignant indications and on the use of non-HCT cell therapies. Bone Marrow Transplant. 2019, 54(10):1575-1585.

    Google Scholar 

  14. Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F, Ruggeri L, Barbabietola G, Aristei C, Latini P, Reisner Y, Martelli MF. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998;339:1186.

    Article  CAS  PubMed  Google Scholar 

  15. Ciceri F, Bonini C, Stanghellini MT, Bondanza A, Traversari C, Salomoni M, Turchetto L, Colombi S, Bernardi M, Peccatori J, Pescarollo A, Servida P, Magnani Z, Perna SK, Valtolina V, Crippa F, Callegaro L, Spoldi E, Crocchiolo R, Fleischhauer K, Ponzoni M, Vago L, Rossini S, Santoro A, Todisco E, Apperley J, Olavarria E, Slavin S, Weissinger EM, Ganser A, Stadler M, Yannaki E, Fassas A, Anagnostopoulos A, Bregni M, Stampino CG, Bruzzi P, Bordignon C. Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I–II study. Lancet Oncol. 2009;10:489.

    Article  PubMed  Google Scholar 

  16. Martelli MF, Ianni MD, Ruggeri L, Falzetti F, Carotti A, Reisner Y, Velardi A. Next generation HLA-haploidentical HSCT. Bone Marrow Transplant. 2015;50:S63.

    Article  CAS  PubMed  Google Scholar 

  17. Di Bartolomeo P, Santarone S, De Angelis G, Picardi A, Cudillo L, Cerretti R, Adorno G, Angelini S, Andreani M, De Felice L, Rapanotti MC, Sarmati L, Bavaro P, Papalinetti G, Di Nicola M, Papola F, Montanari M, Nagler A, Arcese W. Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies. Blood. 2013;121:849–57.

    Article  CAS  PubMed  Google Scholar 

  18. Luznik L, Jalla S, Engstrom LW, Iannone R, Fuchs EJ. Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide. Blood. 2001;98:3456.

    Article  CAS  PubMed  Google Scholar 

  19. Burroughs LM, O’Donnell PV, Sandmaier BM, Storer BE, Luznik L, Symons HJ, Jones RJ, Ambinder RF, Maris MB, Blume KG, Niederwieser DW, Bruno B, Maziarz RT, Pulsipher MA, Petersen FB, Storb R, Fuchs EJ, Maloney DG. Comparison of outcomes of HLA-matched related, unrelated, or HLA-haploidentical related hematopoietic cell transplantation following nonmyeloablative conditioning for relapsed or refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008;14:1279.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kanakry CG, Fuchs EJ, Luznik L. Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev Clin Oncol. 2016;13:10–24.

    Article  CAS  PubMed  Google Scholar 

  21. Duléry R, Bastos J, Paviglianiti A, Malard F, Brissot E, Battipaglia G, Médiavilla C, Giannotti F, Banet A, de Wyngaert ZV, Ledraa T, Belhocine R, Sestili S, Adaeva R, Lapusan S, Isnard F, Legrand O, Vekhoff A, Rubio MT, Ruggeri A, Mohty M. Thiotepa, busulfan, and fludarabine conditioning regimen in T cell-replete HLA-haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019;25:1407.

    Article  CAS  PubMed  Google Scholar 

  22. Bacigalupo A, Laurenti L. Identifying the best Haploidentical donor: are we there? Biol Blood Marrow Transplant. 2018;24:638.

    Article  PubMed  Google Scholar 

  23. Elmariah H, Kasamon YL, Zahurak M, Macfarlane KW, Tucker N, Rosner GL, Bolaños-Meade J, Fuchs EJ, Wagner-Johnston N, Swinnen LJ, Huff CA, Matsui WH, Gladstone DE, McCurdy SR, Borrello I, Gocke CB, Shanbhag S, Cooke KR, Ali SA, Brodsky RA, DeZern AE, Luznik L, Jones RJ, Ambinder RF. Haploidentical bone marrow transplantation with post-transplant cyclophosphamide using non-first-degree related donors. Biol Blood Marrow Transplant. 2018;24:1099.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Nagler A, Rocha V, Labopin M, Unal A, Ben Othman T, Campos A, Volin L, Poire X, Aljurf M, Masszi T, Socie G, Sengelov H, Michallet M, Passweg J, Veelken H, Yakoub-Agha I, Shimoni A, Mohty M. Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission: comparison of intravenous busulfan plus cyclophosphamide (Cy) versus total-body irradiation plus Cy as conditioning regimen—a report from the acute leukemia working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013;31:3549–56.

    Article  CAS  PubMed  Google Scholar 

  25. Cahu X, Labopin M, Giebel S, Aljurf M, Kyrcz-Krzemien S, Socié G, Eder M, Bonifazi F, Bunjes D, Vigouroux S, Michallet M, Stelljes M, Zuckerman T, Finke J, Passweg J, Yakoub-Agha I, Niederwieser D, Sucak G, Sengeløv H, Polge E, Nagler A, Esteve J, Mohty M, Acute leukemia working party of EBMT. Impact of conditioning with TBI in adult patients with T-cell ALL who receive a myeloablative allogeneic stem cell transplantation: a report from the acute leukemia working party of EBMT. Bone Marrow Transplant. 2016;51:351.

    Article  CAS  PubMed  Google Scholar 

  26. Sanz J, Boluda JC, Martín C, González M, Ferrá C, Serrano D, de Heredia CD, Barrenetxea C, Martinez AM, Solano C, Sanz MA, Sanz GF, Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH). Single-unit umbilical cord blood transplantation from unrelated donors in patients with hematological malignancy using busulfan, thiotepa, fludarabine and ATG as myeloablative conditioning regimen. Bone Marrow Transplant. 2012;47(10):1287–93.

    Article  CAS  PubMed  Google Scholar 

  27. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, Apperley J, Slavin S, Pasquini M, Sandmaier BM, Barrett J, Blaise D, Lowski R, Horowitz M. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bacigalupo A, Lamparelli T, Gualandi F, Occhini D, Bregante S, Raiola AM, Ibatici A, di Grazia C, Dominietto A, Piaggio G, Podestà M, Bruno B, Lombardi A, Frassoni F, Viscoli C, Sacchi N, Van Lint MT. Allogeneic hemopoietic stem cell transplants for patients with relapsed acute leukemia: long-term outcome. Bone Marrow Transplant. 2007;39:341–6.

    Article  CAS  PubMed  Google Scholar 

  29. Zeverino M, Agostinelli S, Taccini G, Cavagnetto F, Garelli S, Gusinu M, Vagge S, Barra S, Corvò R. Advances in the implementation of helical tomotherapy-based total marrow irradiation with a novel field junction technique. Med Dosim. 2012;37:314–20.

    Article  PubMed  Google Scholar 

  30. Evens AM, Altman JK, Mittal BB, Hou N, Rademaker A, Patton D, Kaminer L, Williams S, Duffey S, Variakojis D, Singhal S, Tallman MS, Metha J, Winter JN, Gordon I. Phase I/II trial of total lymphoid irradiation and high-dose chemotherapy with autologous stem cell transplantation for relapsed and refractory Hodgkin’s lymphoma. Ann Oncol. 2007;18:679–88.

    Article  CAS  PubMed  Google Scholar 

  31. Moskowitz CH, Yahalom J, Zelenetz AD, Zhang Z, Filippa D, Teruya-Feldstein J, Kewalramani T, Moskowitz AJ, Rice RD, Maragulia J, Vanak J, Trippett T, Hamlin P, Horowitz S, Noy A, O’Connor OA, Portlock C, Straus D, Nimer SD. High-dose chemo-radiotherapy for relapsed or refractory Hodgkin lymphoma and the significance of pre-transplant functional imaging. Br J Haematol. 2010;148:890.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Vagge S, Lamanna G, Vidano G, Ibatici A, Agostinelli S, Carella AM, Corvò R. Volumetric Total lymphoid irradiation: step-up an effective treatment for stem cell transplantation in lymphoma. Radiother Oncol. 2015;115:S403–4.

    Article  Google Scholar 

  33. Shi-Xia X, Xian-Hua T, Hai-Qin X, Bo F, Xiang-Feng T. Total body irradiation plus cyclophosphamide versus busulphan with cyclophosphamide as conditioning regimen for patients with leukemia undergoing allogeneic stem cell transplantation: a meta-analysis. Leuk Lymphoma. 2010;51:50.

    Article  CAS  PubMed  Google Scholar 

  34. Corvò R, Zeverino M, Vagge S, Agostinelli S, Barra S, Taccini G, Van Lint MT, Frassoni F, Bacigalupo A. Helical tomotherapy targeting total bone marrow after total body irradiation for patients with relapsed acute leukemia undergoing an allogeneic stem cell transplant. Radiother Oncol. 2011;98:382–6.

    Article  PubMed  Google Scholar 

  35. Vagge S, Dominietto A, Guolo F, Lemoli R, Bacigalupo A, Angelucci E, Corvò R. Long term report of total marrow or total lymphoid IMRTin advanced leukemia, myeloma and lymphoma. 45th EBMT 2019a, Frankfurt.

    Google Scholar 

  36. Belkacemi Y, Labopin M, Giebel S, Loganadane G, Miszczyk L, Michalett M, Socié G, Schaap N, Cornelissen JJ, Yakoub-Agha I, Polge E, Mothy M, Gorin NC, Nagler A, on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Single-dose daily fractionation is not inferior to twice-a-day fractionated total body irradiation before allogeneic stem cell transplantation for aucte leukemia: a useful practice simplification resulting from the SARASIN study. Int J Radiat Oncol Biol Phys. 2018;102(3):515–26.

    Article  PubMed  Google Scholar 

  37. Paudel N, Schulze D, Gentzler RD, Evens AM, Helenowski I, Dillehay G, Frankfurt O, Metha J, Donnely ED, Gordon LI, Winter JN, Mittal BB. Patterns of failure and survival outcomes after Total Lymphoid Irradiation and high-dose chemotherapy with autologous stem cell transplantation for relapsed or refractory classical Hodgkin lymphoma. Int J Radiat Oncol Biol Phys. 2019;104(2):436–46.

    Article  PubMed  Google Scholar 

  38. Biswas T, Culakova E, Friedberg JW, Kelly JL, Dhakal S, Liesveld J, Phillips GL, Constine LS. Involved field radiation therapy following high dose chemotherapy and autologous stem cell transplant benefits local control and survival in refractory or recurrent Hodgkin lymphoma. Radiother Oncol. 2012;103:367.

    Article  PubMed  Google Scholar 

  39. Rimmer A, Lovie S, Hsu M, Chelius M, Zhang Z, Chau K, Moskowitz CH, Yahalom J. Accelerated total lymphoid irradiation containing salvage regimen for patients with refractory and relapsed Hodgkin lymphoma: 20 years of experience. Int J Radiat Oncol Biol Phys. 2017;97:1066–76.

    Article  Google Scholar 

  40. Gentzler RD, Evens AM, Rademaker AW, Weitner BB, Mittal BB, Dillehay GL, Petrich AM, Altman JK, Frankfurt O, Variakojis D, Singhal S, Metha J, Williams S, Kaminer L, Gordon LI, Winter JN. F-18 FDG-PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Br J Haematol. 2014;165:793–800.

    Article  CAS  PubMed  Google Scholar 

  41. Vagge S, Guolo F, Dominietto A, Agostinelli S, Gusinu M, Ibatici A, Ballerini F, Lemoli RM, Angelucci E, Gobbi M, Corvò R. Helical total lymphoid irradiation: radiotherapy still works in lymphoma transplanatation. Radiother Oncol. 2019b;133:S182.

    Article  Google Scholar 

  42. Raiola A, Dominietto A, Varaldo R, Ghiso A, Galaverna F, Bramanti S, Todisco E, Sarina B, Giordano L, Ibatici A, Santoro A, Clavio M, Bacigalupo A, Castagna L. Unmanipulated haploidentical BMT following non-myeloablative conditioning and post-transplantation CY for advanced Hodgkin’s lymphoma. Biol Blood Marrow Transplant. 2014;49:190.

    Article  CAS  Google Scholar 

  43. Marani C, Raiola AM, Morbelli S, Dominietto A, Ferrarazzo G, Avenoso D, Giannoni L, Varaldo R, Gualandi F, Di Grazia C, Lamparelli T, Bregante S, Van Lint MT, Ibatici A, Bovis F, Lemoli RM, Gobbi M, Bacigalupo A, Angelucci E. Haploidentical transplants with post-transplant cyclophosphamide for relapsed or refractory Hodgkin lymphoma: the role of comorbidity index and pretransplant positron emission tomography. Biol Blood Marrow Transplant. 2018;24:2501–8.

    Article  CAS  PubMed  Google Scholar 

  44. Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, Bregante S, Van Lint MT, Geroldi S, Luchetti S, Ballerini F, Miglino M, Varaldo R, Bacigalupo A. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant. 2013;19:117.

    Article  CAS  PubMed  Google Scholar 

  45. Bacigalupo A, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, Bregante S, Van Lint MT, Geroldi S, Luchetti S, Grasso R, Pozzi S, Colombo N, Tedone E, Varaldo R, Raiola AM. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignances following a myeloablative conditioning: an update. Bone Marrow Transplant. 2015;50:S37.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology and Marrow Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Alida Dominietto

  2. Division of Radiation Oncology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Stefano Vagge

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  1. Alida Dominietto
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Correspondence to Stefano Vagge .

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  1. Department of Radiation Oncology, City Of Hope National Medical Center, Duarte, CA, USA

    Jeffrey Y. C. Wong

  2. Department of Radiation Oncology, City Of Hope National Medical Center, Duarte, CA, USA

    Susanta K. Hui

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Dominietto, A., Vagge, S. (2020). Total Marrow Irradiation and Total Lymphoid Irradiation in Lymphoma and Advanced Hematologic Malignancies: The Genoa Experience. In: Wong, J., Hui, S. (eds) Total Marrow Irradiation. Springer, Cham. https://doi.org/10.1007/978-3-030-38692-4_6

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  • DOI: https://doi.org/10.1007/978-3-030-38692-4_6

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