Acute and late toxicity after Acute and late toxicity after fractionated total body fractionated total body irradiation as conditioning for irradiation as conditioning for bone marrow transplantation bone marrow transplantation L Gocheva Gocheva, K , K Sergieva Sergieva, B , B Avramova Avramova, , L I Koleva Koleva, V , V Vasileva Vasileva, B , B Sultanov Sultanov I Medical University, Sofia, Medical University, Sofia, BULGARIA BULGARIA
During the past 40 years, During the past 40 years, hematopoietic stem cell hematopoietic stem cell transplantation transplantation has been accepted as routine has been accepted as routine treatment for many patients treatment for many patients with neoplastic neoplastic and hereditary with and hereditary diseases. The number of patients diseases. The number of patients receiving transplants has receiving transplants has increased exponentially to increased exponentially to currently about 25,000 per year. currently about 25,000 per year.
Total body irradiation Total body irradiation followed by followed by bone marrow transplantation bone marrow transplantation is well established as a part is well established as a part of the conditioning regimen of the conditioning regimen in high dose therapy. in high dose therapy.
During the last decades high- -dose dose During the last decades high TBI including TBI chemoradiotherapy chemoradiotherapy including has been considered to have a has been considered to have a recognized therapeutic potential in recognized therapeutic potential in acute high- -risk risk acute high LEUKEMIAS LEUKEMIAS and in more than 20 20 other other and in more than indications, including lympho lympho- - and indications, including and myeloproliferative diseases and solid myeloproliferative diseases and solid tumors. tumors.
It is just during the last It is just during the last decade that decade that Bulgarian oncological oncological the Bulgarian the community community has gained a deeper insight has gained a deeper insight and knowledge in the field of and knowledge in the field of HSCT . HSCT .
In Bulgaria In Bulgaria the first autologous autologous BMT BMT was was the first carried out in 1997 1997 , , carried out in the first TBI with TBI with allogeneic allogeneic BMT BMT – – the first in 2002 2002 in and the first allogeneic allogeneic BMT BMT with with and the first nonmyeloablative conditioning nonmyeloablative conditioning regimen including TBI of TBI of 2 2 Gy Gy – – in regimen including in 2005 005 . . 2
OBJECTIVE OBJECTIVE � To report To report � acute late toxicity the acute and late toxicity the and investigated prospectively investigated prospectively in patients with with leukemias leukemias, , in patients Medical University of Sofia, treated at the Medical University of Sofia, treated at the who had conditioning regimes including who had conditioning regimes including fractionated TBI and fractionated TBI and chemotherapy. chemotherapy.
Materials and methods Materials and methods Between Between 2002 2007 January 2002 and December 2007 January and December 18 patients, , 18 patients 11 males 7 females / 11 males and 7 females with / and with 12 years median age 12 years (range 8- -50)/ 50)/ median age (range 8 TBI received TBI in our institution. in our institution. received
Materials and methods Materials and methods INITIAL DIAGNOSIS ALL AML CML 11 (61%) 4 (22%) 3 (17%)
Materials and methods Materials and methods DISEASE STATUS PROGRESSION REMISSION CHRONIC PHASE 4 (22%) 11 (61%) 3 (17%)
Conditioning regimen Conditioning regimen Myeloablative conditioning regimen conditioning regimen Myeloablative melphalan, cyclophosphamide fludarabine, vepesid ATG and TBI 10-12 Gy cyclophosphamide and TBI 10-12 Gy and TBI 10-12 Gy (10) (2) (3)
Conditioning regimen Conditioning regimen Nonmyeloablative conditioning conditioning Nonmyeloablative regimen regimen fludarabine and TBI of 2 Gy (3)
Materials and methods Materials and methods � Large fields treatment stationary Large fields treatment stationary � technique, based on technique, based on Cobalt- -60 unit 60 unit Cobalt and specially designed and specially designed patient table , patient table , movable above and below the floor level, movable above and below the floor level, was used. was used. 80x80 cm2 Field sizes up to 80x80 � Field sizes up to cm2 at at � 300 a SSD 300 cm were achieved. a SSD cm were achieved.
Materials and methods Materials and methods All the patients were conditioned with high- - All the patients were conditioned with high dose chemoradiotherapy chemoradiotherapy regimen dose regimen including a fractionated including a fractionated TBI TBI delivering delivering 10 - - 12 2 10 12 2 Gy Gy Gy Gy in in in in 15 (73%) 3 (17%). ). 15 (73%) 3 (17%
Materials and methods Materials and methods FRACTIONATED TBI 10 – 12 Gy 10 Gy 12 Gy 10 Gy 5fr/5d 6fr/3d 6fr/3d 8 (44%) 2 (11%) 5 (28%)
Materials and methods Materials and methods dose rate The requirement for dose rate � The requirement for � of 5 - - 10 10 cGy cGy/min was adhered /min was adhered of 5 to. to. lung shields were Personalized lung shields � Personalized were � used to compensate different used to compensate different density and to reduce the lung density and to reduce the lung dose to 8 Gy Gy. . dose to 8
Materials and methods Materials and methods � The received radiation doses to The received radiation doses to � various parts of the body are various parts of the body are monitored by monitored by in vivo dosimetry dosimetry in vivo using semiconductor detectors using semiconductor detectors placed anteriorly anteriorly and postreiorly postreiorly placed and on a number of specified body on a number of specified body sites. sites.
Materials and methods Materials and methods 13 In 13 (72%) patients transplantation was carried In (72%) patients transplantation was carried HLA- -identical related donor identical related donor out from HLA out from 5 and in 5 unrelated donor. . from unrelated donor (28%) – – and in (28%) from 18 allogeneic From the performed 18 allogeneic From the performed 17 transplantations 17 peripheral were of peripheral transplantations were of blood stem cells 1 bone blood stem cells and 1 of bone – and – of marrow stem cells. . marrow stem cells
Materials and methods Materials and methods Posttransplantation clinical, Posttransplantation clinical, biologic, and functional biologic, and functional evaluations were performed evaluations were performed on on days 30, 100, 180, year 1 , days 30, 100, 180, year 1 , and annually thereafter. and annually thereafter.
Materials and methods Materials and methods Each evaluation included an Each evaluation included an assessment of the study end points: assessment of the study end points: marrow chimerism chimerism, , � marrow � treatment- -related toxicity, related toxicity, � treatment � treatment related mortality � treatment related mortality � graft- -versus versus- -host host- -disease disease . � graft . �
Materials and methods Materials and methods The assessment The assessment of the early of the early and late reactions was made and late reactions was made using using the adverse event severity the adverse event severity scale of CTC АЕ АЕ v.3 .3 NCI NCI , scale of CTC v , USA. USA.
RESULTS RESULTS Median follow- -up up Median follow from BMT was from BMT was 27 months 27 months (range 3- -52). 52). (range 3
RESULTS RESULTS Premedication Premedication was carried out in all patients including was carried out in all patients including antiemetics antiemetics (mainly serotonin receptor (mainly serotonin receptor antagonists – – ondansetron ondansetron, , granisetron granisetron, , antagonists tropisetron) and ) and tropisetron corticosteroids corticosteroids (8 8 to to 20 20 mg) mg). . (
RESULTS RESULTS During the transplantation period on During the transplantation period on day 0 and +1 the realized day 0 and +1 the realized transplantation of the donor cells transplantation of the donor cells pool passed pool passed 16 in 16 without complications without complications of the in of the patients and was accompanied by patients and was accompanied by allergic reactions 2 patients. allergic reactions in 2 patients. in
RESULTS RESULTS bone- -marrow marrow aplasia aplasia Induced bone � Induced � all patients during was observed in all patients during was observed in the post- -transplantation period. transplantation period. the post engraftment ” “ engraftment � On day On day +14 +14 to to +24 +24 “ ” � 16 patients. was established in 16 patients. was established in 2 patients no symptoms of the grafting In 2 � In patients no symptoms of the grafting � were observed, which imposed were observed, which imposed reinfusion of donor cells pool. reinfusion of donor cells pool.
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