Acute and late toxicity after Acute and late toxicity after - - PowerPoint PPT Presentation

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 L Gocheva Gocheva, K , K Sergieva Sergieva, B , B Avramova Avramova, , I I Koleva Koleva, V , V Vasileva Vasileva, B , B Sultanov Sultanov

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 with neoplastic neoplastic and hereditary 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

• f the conditioning regimen
• f the conditioning regimen

in high dose therapy. in high dose therapy.

During the last decades high During the last decades high-

• dose

dose chemoradiotherapy chemoradiotherapy including including TBI

TBI

has been considered to have a has been considered to have a recognized therapeutic potential in recognized therapeutic potential in acute high acute high-

• risk

risk

LEUKEMIAS LEUKEMIAS

and in more than and in more than 20 20 other

• ther

indications, including indications, including lympho lympho-

• and

and myeloproliferative myeloproliferative diseases and solid diseases and solid tumors. tumors.

It is just during the last It is just during the last decade that decade that the the Bulgarian

Bulgarian oncological

• ncological

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 the first autologous autologous BMT BMT was was carried out in carried out in 1997 1997, , the first the first TBI with TBI with allogeneic allogeneic BMT BMT – – in in 2002 2002 and the first and the first allogeneic allogeneic BMT BMT with with nonmyeloablative nonmyeloablative conditioning conditioning regimen including regimen including TBI of TBI of 2 2 Gy Gy – – in in 2 2005 005. .

OBJECTIVE OBJECTIVE

• To report

To report the the acute

acute

and and late toxicity

late toxicity

investigated prospectively investigated prospectively

in patients in patients with with leukemias leukemias, ,

treated at the treated at the Medical University of Sofia,

Medical University of Sofia, 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 January January 2002

2002

and December and December 2007

2007 18 patients 18 patients, ,

/ /11 males

11 males

and and 7 females

7 females

with with median age median age 12 years

12 years

(range 8 (range 8-

• 50)/

50)/ received received TBI

TBI

in our institution. in our institution.

Materials and methods Materials and methods

INITIAL DIAGNOSIS

ALL 11 (61%) AML 4 (22%) CML 3 (17%)

Materials and methods Materials and methods

DISEASE STATUS

REMISSION

11 (61%)

PROGRESSION

4 (22%)

CHRONIC PHASE

3 (17%)

Conditioning regimen Conditioning regimen

Myeloablative Myeloablative conditioning regimen conditioning regimen

cyclophosphamide vepesid and TBI 10-12 Gy (10) cyclophosphamide and TBI 10-12 Gy (3) melphalan, fludarabine, ATG and TBI 10-12 Gy (2)

Conditioning regimen Conditioning regimen

Nonmyeloablative Nonmyeloablative conditioning conditioning 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 Cobalt-

• 60 unit

60 unit

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.

• Field sizes up to

Field sizes up to 80x80

80x80 cm2

cm2 at at a SSD a SSD 300

300

cm were achieved. cm were achieved.

Materials and methods Materials and methods

All the patients were conditioned with high All the patients were conditioned with high-

• dose

dose chemoradiotherapy chemoradiotherapy regimen regimen including a fractionated including a fractionated

TBI TBI

delivering delivering

10 10 -

• 12

12

Gy Gy

2 2

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

5fr/5d 2 (11%)

10 Gy

6fr/3d 5 (28%)

12 Gy

6fr/3d 8 (44%)

Materials and methods Materials and methods

• The requirement for

The requirement for dose rate

dose rate

• f 5
• f 5 -
• 10

10 cGy cGy/min was adhered /min was adhered to. to.

• Personalized

Personalized lung shields

lung shields were

were used to compensate different used to compensate different density and to reduce the lung density and to reduce the lung dose to 8 dose to 8 Gy Gy. .

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 in vivo dosimetry dosimetry

using semiconductor detectors using semiconductor detectors placed placed anteriorly anteriorly and and postreiorly postreiorly

• n a number of specified body
• n a number of specified body

sites. sites.

Materials and methods Materials and methods

In In 13

13

(72%) patients transplantation was carried (72%) patients transplantation was carried

• ut from
• ut from HLA

HLA-

• identical related donor

identical related donor

and in and in 5

5

(28%) (28%) – – from from unrelated donor

unrelated donor. .

From the performed From the performed 18

18 allogeneic

allogeneic transplantations transplantations 17

17

were of were of peripheral

peripheral blood stem cells blood stem cells

and and 1

1

– –

• f
• f bone

bone marrow stem cells marrow stem cells. .

Materials and methods Materials and methods

Posttransplantation Posttransplantation clinical, clinical, biologic, and functional biologic, and functional evaluations were performed evaluations were performed

• n
• n

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

marrow chimerism chimerism, ,

• treatment

treatment-

• related toxicity,

related toxicity,

• treatment related mortality

treatment related mortality

• graft

graft-

• versus

versus-

• host

host-

• disease

disease.

.

Materials and methods Materials and methods

The assessment The assessment

• f the early
• f 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 scale of CTCАЕ АЕ v v.3 .3 NCI NCI,

, USA. USA.

RESULTS RESULTS

Median follow Median follow-

• up

up

from BMT was from BMT was

27 months 27 months (range 3 (range 3-

• 52).

52).

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 antagonists – – ondansetron

• ndansetron,

, granisetron granisetron, , tropisetron tropisetron) and ) and

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

without complications without complications

in in 16

16

• f the
• f the

patients and was accompanied by patients and was accompanied by

allergic reactions allergic reactions

in in 2

2 patients.

patients.

RESULTS RESULTS

• Induced

Induced bone

bone-

• marrow

marrow aplasia aplasia

was observed in was observed in all patients

all patients during

during the post the post-

• transplantation period.

transplantation period.

• On day

On day +14 +14 to to +24 +24 “ “engraftment

engraftment”

” was established in was established in 16

16 patients.

patients.

• In

In 2

2 patients no symptoms of the grafting

patients no symptoms of the grafting were observed, which imposed were observed, which imposed

reinfusion reinfusion of donor cells pool.

• f donor cells pool.

RESULTS RESULTS

The most frequent The most frequent reactions determining reactions determining

acute acute toxicity toxicity

due to the conditioning due to the conditioning regimens and the regimens and the induced bone induced bone-

• marrow

marrow aplasia aplasia, are , are Indisposition Indisposition 93 % 93 % Fatigue Fatigue syndrome syndrome 68 % 68 % Headache Headache 16 % 16 % Loss of appetite Loss of appetite 58 % 58 % Nausea Nausea 7 75 % 5 % Emesis Emesis 58 % 58 % Mucositis Mucositis 50 % 50 % Oesophagitis Oesophagitis 8 % 8 % Diarrhea Diarrhea 50 % 50 % Parotitis Parotitis 8 % 8 % Pruritus Pruritus 33 % 33 %

ACUTE TOXICITY ACUTE TOXICITY

Acute organ toxicity Acute organ toxicity

was recorded in was recorded in

11 patients 11 patients

during the 6 during the 6-

• year period of

year period of clinical observation clinical observation.

.

ACUTE TOXICITY ACUTE TOXICITY

Acute GvHD

(7) IDIOPATHIC PHEUMONIA SYNDROME (2) LIVER TOXICITY (1) NEUROLO- GICAL TOXICITY (1)

RESULTS RESULTS

No development No development

• f
• f

cardiovascular, cardiovascular, renal renal

• r
• r
• ther type
• ther type
• f acute organ
• f acute organ

toxicity was established. toxicity was established.

LATE TOXICITY LATE TOXICITY

Late toxicity Late toxicity

was recorded in was recorded in

8 patients 8 patients

during the 6 during the 6-

• year period of

year period of clinical observation. clinical observation.

LATE TOXICITY LATE TOXICITY

Cataract (1) Liver Toxicity (1) Chronic GvHD (6)

LATE TOXICITY LATE TOXICITY

In all the In all the 6

6

patients patients

late late GvHD GvHD

was successfully controlled was successfully controlled

and it was not the reason for the and it was not the reason for the fatal outcome in neither of these fatal outcome in neither of these patients. patients.

Fatal organ toxicity Fatal organ toxicity

Fatal organ toxicity Fatal organ toxicity

was found in was found in

5 patients. 5 patients.

Fatal organ toxicity Fatal organ toxicity

Acute GvHD (2) Idiopathic pneumonia syndrome (1) Liver toxicity (1) Neurological toxicity (1)

CONCLUSION CONCLUSION

• FTBI is a

FTBI is a well tolerated

well tolerated

therapeutic regimen in high therapeutic regimen in high dose therapy. dose therapy.

• The observed acute and late

The observed acute and late toxicity in the 18 patients is toxicity in the 18 patients is

similar similar to the cited in

to the cited in reference literature. reference literature.

CONCLUSION CONCLUSION

• The small number of cases

The small number of cases precludes definitive precludes definitive conclusion of the efficacy conclusion of the efficacy

• f the regimens used and
• f the regimens used and

further evaluation is further evaluation is required. required.

THANK YOU THANK YOU FOR FOR YOUR ATTENTION YOUR ATTENTION