Copyright
0360.3016/YO $3.00 + .OO cc I990 Pergamon Press plc
??Original Contribution
FRACTIONATED TOTAL BODY IRRADIATION AND BONE MARROW TRANSPLANTATION IN ACUTE LYMPHOBLASTIC LEUKEMIA M.D., M. RESBEUT,
C. ALTSCHULER,
A. M. STOPPA,
M.D.,
M.D.,
D. BLAISE,
J. L. LAGRANGE,
AND
M.D.,
Y. CARCASSONNE,
M.D.,
D. MARANINCHI,
J. P. GUILLET,
M.D.,
PH.D.
M.D.
Institut J. Paoli, I. Calmettes. Marseille, France From March 1982 to September 1988, 108 patients with acute lymphoblastic leukemia (ALL) were conditioned before allogeneic (57 patients of whom 16 T-depleted) or before autologous (51 patients) bone marrow transplantation (BMT). BMT was realized in 66 patients (31 allogeneic and 35 autologous) in first complete remission (CR) and in 42 patients (26 allogeneic and 16 autologous) in second CR or greater or in relapse. All patients received high doses of alkylating agents prior to a low-dose fractionated total body irradiation of 11 Gy in 5 fractions and 5 days. Rejection and relapse rate are described in relation to the three BMT types, allogeneic non T-depleted, allogeneic T-depleted, and autologous, and to the status of the patient at the time of the transplantation. Leukemic deaths are detailed according to the same parameters. Non-leukemic deaths and complications are determined. For the allogeneic population, the 4-year disease-free survival (DFS) is 47%; it is 68.5% in first CR patients, 23.5% in second or subsequent CR patients, and 50% in T-depleted BMT. For the autologous population, 4-year DFS is 35.7%; it is 52% in first CR patients and 30% in patients in second CR or greater. The conditioning regimen appears to be efficient in terms of disease control with a low rate of complications for the non T-depleted population, transplanted in first CR, but has to be improved for the other patients. Acute lymphoblastic
leukemia, Bone marrow transplantation.
of whom were T-depleted) or autologous in 5 1 cases. Allogeneic BMT was performed in 3 1 patients in first CR ( 11 of whom were T-depleted) and in 26 patients in second or subsequent remission or in relapse (6 of whom were T-depleted). Autologous BMT was realized in 35 patients in first CR and in 16 patients in second or subsequent CR. BMT was proposed in adults with first CR as an early consolidation and in children (before 15 years) in the case of translocation (9;22 or 4; 11) of initial white blood count higher than 100,000 and when first CR was not obtained within the month following induction chemotherapy. This series included 40 children, before 15 years (Fig. 1). Median age was 7 years for children (2- 14.9) and 23 for adults ( 15-47). All patients were given chemotherapy prior to irradiation: 42 were conditioned with cyclophosphamide (60 mg/kg/day) for 2 consecutive days, the last infusion given 3 days before total body irradiation (TBI) was started; 59 received melphalan (140 mg/m2), 48 hr before the beginning of TBI; 7 were given these two alkylating agents. All patients received low-dose fractionated TBI and were treated with 18 MeV photons in a semifetal right or left position according to the minimal me-
INTRODUCTION From March 1982 to September 1988, 108 patients with acute lymphoblastic leukemia (ALL) were conditioned before allogeneic or before autologous bone marrow transplantation (BMT). BMT was realized in 66 patients in first complete remission (CR) and in 42 patients in second or greater remission or in relapse. All patients received high doses of alkylating agents prior to a low dose fractionated total body irradiation (TBI) of 1 1 Gy in 5 fractions and 5 days. Rejection and relapse rate are described in relation to the BMT type and to the status of the patient at the time of the transplant. Leukemic deaths are detailed according to the same parameters. Non-leukemic deaths and complications are determined. The disease-free survival is reported according to the different types of BMT.
METHODS
AND
MATERIALS
From March 1982 to September 1988, 108 patients with ALL received BMT either allogeneic in 57 cases ( 16
Accepted for publication
Reprint requests to: C. Altschuler, Service de Radiotherapie, lnstitut J. Paoli. I. Calmettes, 232 Boulevard de Sainte Marguerite F- 13273, Marseille Cedex 9. France. 1151
24 May 1990.
1152
1. J. Radiation Oncology 0 Biology 0 Physics
November 1990, Volume 19, Number 5
6#‘/1 i
* +I___ Ilax
20x !J ;_:
1
i-L
+
_. l_.._,_
I__..
-..+---.-3
IN=571
3 IN=a : > cno
T
L____________..____~_.____ . ..__‘_.___-__&_
8 MONTHS
45 MONTHS
Fig. 2. Probability of persistent CR after allogeneic BMT. Curve 1 = whole allogeneic population. Curve 2 = first CR patients. Curve 3 = second or greater CR patients. Curve 4 = T-depleted population.
Fig. 1. Population according years or > 15 years.
to pre-BMT
status and age < 15
diastinum shift shown on a previous CT scan, using antero-posterior parallel, equally weighted fields. The total dose was 11 Gy given in 5 daily fractions of 2.20 Gy. The dose specification point was determined at the level of umbilicus. Dose monitoring was assured during every fraction by an ionization chamber, located in a small plastic phantom under the treatment couch; previous serial measurements had been realized in this small phantom and a 30 X 30 cm plastic phantom of thickness ranging from 10 to 30 cm, assimilated to the patient abdomen, in relation to the larger phantom thickness. Thus, dose measurement in the small phantom reflects the absolute dose at mid-depth of the patient. In viva dosimetry was realized by semi-conductors diodes, placed by pairs directly on the patient, in five main corresponding areas. The instantaneous dose rate was 15 cGy per minute and the averaged dose rate was 4 cGy/min until November 1987 and then 20 and 8 cGy/min, respectively. Lungs were shielded for 2 fractions, on days 3 and 4, with 5 half value layer blocks in anterior and posterior position for each of these 2 days, without chest wall electron boost. The median lung dose was 7.4 Gy. Male patients were given a testicular electron boost: 6 Gy in 3 fractions after the 100th day following BMT until December 1987 and then 4 Gy delivered in 1 fraction during the last TBI session.
tation. In the case of first CR, relapse was evidenced in 2/3 1 allogeneic grafts (6.4%) both T-depleted and in lO/ 35 autologous (28.4%). In patients transplanted after first CR, relapse rate was 50% (13/26) in allogeneic BMT and 62% (10/16) in autologous. In T-depleted BMT, relapse occurred in 5/16 patients: two in first CR and three in relapse. Leukemic deaths occurred in 26 patients. In first CR (66 cases), 11 patients died from relapse (2 T-depleted allogeneic and 9 autologous) and after first CR (42 cases), 14 patients (7 allogeneic, 2 T-depleted allogeneic, and 5 autologous). Five patients died from severe GVHD and seven from early bacterial/fungal infection (4 allogeneic and 3 autologous BMT) whereas three patients died from viral/interstitial pneumonitis after allogeneic BMT. Three patients died from AIDS (2 allogeneic and 1 autologous grafts). Regarding lung complications, nine patients died with extensive pneumonia: five early after BMT during bacteremia or fungal infection, and four late after BMT, one of whom associated with AIDS and two associated with GVHD. Veno-occlusive disease of the liver (VOD) occurred in five patients but was not the primary cause of death since it was always associated with overwhelming bacterial/ fungal infection.
RESULTS Engraftment occurred in all patients receiving non Tdepleted BMT, except in two patients who died within the first month following the graft, that is, before it could be demonstrated. In the 16 T-depleted BMT, five rejections (3 1%) were observed, all in first CR patients. Only one engraftment failed in autologous transplantations. Relapse rate was different according to the BMT type and the status of the patient at the moment of the transplan-
j % L___---____.___-__is_____ B MONTHS
_-.________L_
9u MONTHS
Fig. 3. Disease-free survival after allogeneic BMT. Curve 1 = whole allogeneic population. Curve 2 = first CR patients. Curve 3 = second or subsequent CR patients. Curve 4 = Tdepleted population.
Fractionated TBI and bone marrow transplantation 0 C. ALTSC‘HLJLERPI d.
80 %
60 % 48x L--C--.
20x
------i
20z
3 ()r=(, ; >m()
g %
’
-____._ +_ Qz I --_-_-_.-_-e-. -- _ .__+-.m-_-..___ 0 MONTHS xi 90 MONTHS Fig. 4. Probability of persistent CR after autologous BMT. Curve 1 = whole autologous population. Curve 2 = first CR patients. Curve 3 = second or greater CR patients.
Encephalitis, probably due to CMV, was observed in two patients. In allogeneic BMT, 4-year overall survival rate is 53% for the whole population: it is 68.5% in first CR patients, 34% in patients after first CR, and 50% for T-depleted grafts. The probability to remain in complete remission after the graft is, respectively, 69%, 93%, 41%, and 7 1% (Fig. 2). Disease-free survival in the same conditions is 47%, 68.5%, 23.5%, and 50% (Fig. 3). In autologous BMT, the 4-year overall survival rate is also 53% in all patients. It is 57% in first CR patients and 53% patients after first CR. The probability of persistent remission after autologous BMT is, respectively, 49%, 56.4%, and 32% (Fig. 4). Disease-free survival in this population is, respectively, 35.7%, 52%, and 30% (Fig. 5). DISCUSSION There is controversy in the treatment of ALL after the obtention of first CR, particularly in children (1, 3, 7). One prospective study ( 10) compared maintenance chemotherapy and allogeneic transplantation and indicated a reduced rate of relapse in the transplanted group. Another study (6) compared allogeneic and autologous BMT, with an advantage for the allogeneic population in terms of relapse but a higher transplantation related morbidity in the allogeneic group. The introduction of T-depletion, in order to reduce toxicity associated with transplantation procedures, has
i
.~3q.+__‘L_, it -+---p+*-_:____
t t I
1153
2 (II =36:CRll - t+ C-A. I : _-_+----_--__-__ +L-_-_ 1 IN=61) 3 (II= la : XRl)
L_--_ @ MONTHS
___--
__&
-_-_-_t_
38 MONTHS
Fig. 5. Disease-free survival after autologous BMT. Curve I = whole autologous population. Curve 2 = first CR patients. Curve 3 = second or subsequent CR patients.
not resulted in an improved survival rate, with a higher rate of relapse and rejection (2, 7); this may be because of the lack of a “graft-versus-leukemia” effect (8) and might require an intensified preparative regimen, perhaps hyperfractionated TBI (2, 5). On the other hand, most techniques of marrow ablation associate TBI and high dose chemotherapy, and their respective timing might play a role particularly in relapse patients (4, 9). In this retrospective non-randomized study, the results are satisfying in terms of leukemic relapse and survival rate for the allogeneic non T-depleted BMT, performed in first CR, whereas there is a higher risk of relapse in Tdepleted allogeneic and in autologous BMT, performed in second or greater CR. This non-randomized study leads us to believe that an intensification of the conditioning regimen is not necessary in the first CR patients, since we did not observe too many radiation related complications with less than 5% of interstitial pneumonitis and VOD, and with a correct disease control (4-year DFS = 68.5%). Furthermore, immunosuppression of this TBI is efficient without any rejection in non T-depleted patients. This encouraged us to perform the allogeneic BMT in patients with a HLAidentical donor when possible, early in the evolution of the disease. On the other hand, results are very dismal when BMT is not performed in first CR. In this case, we have to improve the conditioning regimen without increasing the complications related to the transplantation.
REFERENCES I. Bordigoni, P.; Vernant, J. P.; Gluckman, E.; Maraninchi, D.; Milpied, N.; Fischer, A.; Lemoine, E. Benz; Jouet, J. P.; Reiffers, J. Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in first remission: a cooperative study of the Groupe d’Etude de la Greffe de Moelle Osseuse. J. Clin. Oncol. 7(6):747-753; 1989. 2. Champlain, R. E.; Ho, W. G.; Mitsuyasu, R.; Burnison, M.; Greenberg, P.; Holly, G.; Winston, D. W.; Feig, S. A.; Gale,
R. P. Graft failure and leukemia relapse following T-lymphocyte-depleted bone marrow transplants: effect of intensification of immuno-suppressive conditioning. Transplant. Proc. X1X( 1):2616-2619; 1987. R.; Gale, R. P. Bone marrow transplantation 3. Champlain, for acute leukemia: recent advances and comparison with alternative therapies. Sem. Hematol. 24( 1):55-67; 1987. H. G.; Philips, G. L. A guide to 4. Deeg, H. J.; Klingemann, bone marrow transplantation. Berlin: Springer-Verlag; 1988.
I. J. Radiation Oncology 0 Biology 0 Physics
1154
Guyotat, D.; Dutou, L.; Ehrsam, A.; Campos, I.; Archimbaud, E.; Fiere, D. Graft rejection after T-cell depleted marrow transplantation: role of fractionated irradiation. Br. J. Haematol. 65499; 1987.
Kersey, J. H.; Weisdorf, D.; Nesbit, M. E.; Lebien, T. W.; Woods, W. G.; Mac Glave, P. B.; Kim, T.; Vallera, D. A.; Goldman, A. I.; Bostrom, B.; Hurd, D.; Ramsay, N. K. C. Comparison of autologous and allogeneic bone marrow transplantation for treatment of high-risk refractory acute lymphoblastic leukemia. N. Eng. J. Med. 3 17(8):46 l-467; 1987. Mayer, R. J. chemotherapy “best choice”? Odom, L. F.;
Allogeneic transplantation versus intensive in first remission acute leukemia: is there a J. Clin. Oncol. 6( 10): 1532- 1536; 1988. August, C. S.; Githens, J. H. Remission of
November 1990, Volume 19, Number 5
relapsed leukemia during a graft versus host reaction. A “graft versus leukemia reaction” in man. Lancet 2:537-540; 1978. 9. Shank, B.; Chu, F. C.; Dinsmore, R.; Kappor, N.; Kirkpatrick, D.; Teitelbaum, H.; Reid, A.; Bonfiglio, P.; Simpson, L.; O’Reilly, R. J. Hyperfractionated total body irradiation for bone marrow transplantation. Results in 70 leukemia patients with allogeneic transplants. Int. J. Radiat. Oncol. Biol. Phys. 9: 1607- 16 11; 1983. 10. Zander, A. R.; Keating, M.; Dicke, K.; Dixon, D.; Pierce, S.; Jagannath, S.; Peters, L.; Horwitz, L.; Cockerill, K.; Spitzer, G.; Vellekoop, L.; Kantarjian, H.; Walters, R.; Mac Credie, K.; Freireich, E. J. A comparison of marrow transplantation with chemotherapy for adults with acute leukemia of poor prognosis in first complete remission. J. Clin. Oncol. 6( 10):1548-1557; 1988.
0360.3016/YO $3.00 + .OO cc I990 Pergamon Press plc
??Original Contribution
FRACTIONATED TOTAL BODY IRRADIATION AND BONE MARROW TRANSPLANTATION IN ACUTE LYMPHOBLASTIC LEUKEMIA M.D., M. RESBEUT,
C. ALTSCHULER,
A. M. STOPPA,
M.D.,
M.D.,
D. BLAISE,
J. L. LAGRANGE,
AND
M.D.,
Y. CARCASSONNE,
M.D.,
D. MARANINCHI,
J. P. GUILLET,
M.D.,
PH.D.
M.D.
Institut J. Paoli, I. Calmettes. Marseille, France From March 1982 to September 1988, 108 patients with acute lymphoblastic leukemia (ALL) were conditioned before allogeneic (57 patients of whom 16 T-depleted) or before autologous (51 patients) bone marrow transplantation (BMT). BMT was realized in 66 patients (31 allogeneic and 35 autologous) in first complete remission (CR) and in 42 patients (26 allogeneic and 16 autologous) in second CR or greater or in relapse. All patients received high doses of alkylating agents prior to a low-dose fractionated total body irradiation of 11 Gy in 5 fractions and 5 days. Rejection and relapse rate are described in relation to the three BMT types, allogeneic non T-depleted, allogeneic T-depleted, and autologous, and to the status of the patient at the time of the transplantation. Leukemic deaths are detailed according to the same parameters. Non-leukemic deaths and complications are determined. For the allogeneic population, the 4-year disease-free survival (DFS) is 47%; it is 68.5% in first CR patients, 23.5% in second or subsequent CR patients, and 50% in T-depleted BMT. For the autologous population, 4-year DFS is 35.7%; it is 52% in first CR patients and 30% in patients in second CR or greater. The conditioning regimen appears to be efficient in terms of disease control with a low rate of complications for the non T-depleted population, transplanted in first CR, but has to be improved for the other patients. Acute lymphoblastic
leukemia, Bone marrow transplantation.
of whom were T-depleted) or autologous in 5 1 cases. Allogeneic BMT was performed in 3 1 patients in first CR ( 11 of whom were T-depleted) and in 26 patients in second or subsequent remission or in relapse (6 of whom were T-depleted). Autologous BMT was realized in 35 patients in first CR and in 16 patients in second or subsequent CR. BMT was proposed in adults with first CR as an early consolidation and in children (before 15 years) in the case of translocation (9;22 or 4; 11) of initial white blood count higher than 100,000 and when first CR was not obtained within the month following induction chemotherapy. This series included 40 children, before 15 years (Fig. 1). Median age was 7 years for children (2- 14.9) and 23 for adults ( 15-47). All patients were given chemotherapy prior to irradiation: 42 were conditioned with cyclophosphamide (60 mg/kg/day) for 2 consecutive days, the last infusion given 3 days before total body irradiation (TBI) was started; 59 received melphalan (140 mg/m2), 48 hr before the beginning of TBI; 7 were given these two alkylating agents. All patients received low-dose fractionated TBI and were treated with 18 MeV photons in a semifetal right or left position according to the minimal me-
INTRODUCTION From March 1982 to September 1988, 108 patients with acute lymphoblastic leukemia (ALL) were conditioned before allogeneic or before autologous bone marrow transplantation (BMT). BMT was realized in 66 patients in first complete remission (CR) and in 42 patients in second or greater remission or in relapse. All patients received high doses of alkylating agents prior to a low dose fractionated total body irradiation (TBI) of 1 1 Gy in 5 fractions and 5 days. Rejection and relapse rate are described in relation to the BMT type and to the status of the patient at the time of the transplant. Leukemic deaths are detailed according to the same parameters. Non-leukemic deaths and complications are determined. The disease-free survival is reported according to the different types of BMT.
METHODS
AND
MATERIALS
From March 1982 to September 1988, 108 patients with ALL received BMT either allogeneic in 57 cases ( 16
Accepted for publication
Reprint requests to: C. Altschuler, Service de Radiotherapie, lnstitut J. Paoli. I. Calmettes, 232 Boulevard de Sainte Marguerite F- 13273, Marseille Cedex 9. France. 1151
24 May 1990.
1152
1. J. Radiation Oncology 0 Biology 0 Physics
November 1990, Volume 19, Number 5
6#‘/1 i
* +I___ Ilax
20x !J ;_:
1
i-L
+
_. l_.._,_
I__..
-..+---.-3
IN=571
3 IN=a : > cno
T
L____________..____~_.____ . ..__‘_.___-__&_
8 MONTHS
45 MONTHS
Fig. 2. Probability of persistent CR after allogeneic BMT. Curve 1 = whole allogeneic population. Curve 2 = first CR patients. Curve 3 = second or greater CR patients. Curve 4 = T-depleted population.
Fig. 1. Population according years or > 15 years.
to pre-BMT
status and age < 15
diastinum shift shown on a previous CT scan, using antero-posterior parallel, equally weighted fields. The total dose was 11 Gy given in 5 daily fractions of 2.20 Gy. The dose specification point was determined at the level of umbilicus. Dose monitoring was assured during every fraction by an ionization chamber, located in a small plastic phantom under the treatment couch; previous serial measurements had been realized in this small phantom and a 30 X 30 cm plastic phantom of thickness ranging from 10 to 30 cm, assimilated to the patient abdomen, in relation to the larger phantom thickness. Thus, dose measurement in the small phantom reflects the absolute dose at mid-depth of the patient. In viva dosimetry was realized by semi-conductors diodes, placed by pairs directly on the patient, in five main corresponding areas. The instantaneous dose rate was 15 cGy per minute and the averaged dose rate was 4 cGy/min until November 1987 and then 20 and 8 cGy/min, respectively. Lungs were shielded for 2 fractions, on days 3 and 4, with 5 half value layer blocks in anterior and posterior position for each of these 2 days, without chest wall electron boost. The median lung dose was 7.4 Gy. Male patients were given a testicular electron boost: 6 Gy in 3 fractions after the 100th day following BMT until December 1987 and then 4 Gy delivered in 1 fraction during the last TBI session.
tation. In the case of first CR, relapse was evidenced in 2/3 1 allogeneic grafts (6.4%) both T-depleted and in lO/ 35 autologous (28.4%). In patients transplanted after first CR, relapse rate was 50% (13/26) in allogeneic BMT and 62% (10/16) in autologous. In T-depleted BMT, relapse occurred in 5/16 patients: two in first CR and three in relapse. Leukemic deaths occurred in 26 patients. In first CR (66 cases), 11 patients died from relapse (2 T-depleted allogeneic and 9 autologous) and after first CR (42 cases), 14 patients (7 allogeneic, 2 T-depleted allogeneic, and 5 autologous). Five patients died from severe GVHD and seven from early bacterial/fungal infection (4 allogeneic and 3 autologous BMT) whereas three patients died from viral/interstitial pneumonitis after allogeneic BMT. Three patients died from AIDS (2 allogeneic and 1 autologous grafts). Regarding lung complications, nine patients died with extensive pneumonia: five early after BMT during bacteremia or fungal infection, and four late after BMT, one of whom associated with AIDS and two associated with GVHD. Veno-occlusive disease of the liver (VOD) occurred in five patients but was not the primary cause of death since it was always associated with overwhelming bacterial/ fungal infection.
RESULTS Engraftment occurred in all patients receiving non Tdepleted BMT, except in two patients who died within the first month following the graft, that is, before it could be demonstrated. In the 16 T-depleted BMT, five rejections (3 1%) were observed, all in first CR patients. Only one engraftment failed in autologous transplantations. Relapse rate was different according to the BMT type and the status of the patient at the moment of the transplan-
j % L___---____.___-__is_____ B MONTHS
_-.________L_
9u MONTHS
Fig. 3. Disease-free survival after allogeneic BMT. Curve 1 = whole allogeneic population. Curve 2 = first CR patients. Curve 3 = second or subsequent CR patients. Curve 4 = Tdepleted population.
Fractionated TBI and bone marrow transplantation 0 C. ALTSC‘HLJLERPI d.
80 %
60 % 48x L--C--.
20x
------i
20z
3 ()r=(, ; >m()
g %
’
-____._ +_ Qz I --_-_-_.-_-e-. -- _ .__+-.m-_-..___ 0 MONTHS xi 90 MONTHS Fig. 4. Probability of persistent CR after autologous BMT. Curve 1 = whole autologous population. Curve 2 = first CR patients. Curve 3 = second or greater CR patients.
Encephalitis, probably due to CMV, was observed in two patients. In allogeneic BMT, 4-year overall survival rate is 53% for the whole population: it is 68.5% in first CR patients, 34% in patients after first CR, and 50% for T-depleted grafts. The probability to remain in complete remission after the graft is, respectively, 69%, 93%, 41%, and 7 1% (Fig. 2). Disease-free survival in the same conditions is 47%, 68.5%, 23.5%, and 50% (Fig. 3). In autologous BMT, the 4-year overall survival rate is also 53% in all patients. It is 57% in first CR patients and 53% patients after first CR. The probability of persistent remission after autologous BMT is, respectively, 49%, 56.4%, and 32% (Fig. 4). Disease-free survival in this population is, respectively, 35.7%, 52%, and 30% (Fig. 5). DISCUSSION There is controversy in the treatment of ALL after the obtention of first CR, particularly in children (1, 3, 7). One prospective study ( 10) compared maintenance chemotherapy and allogeneic transplantation and indicated a reduced rate of relapse in the transplanted group. Another study (6) compared allogeneic and autologous BMT, with an advantage for the allogeneic population in terms of relapse but a higher transplantation related morbidity in the allogeneic group. The introduction of T-depletion, in order to reduce toxicity associated with transplantation procedures, has
i
.~3q.+__‘L_, it -+---p+*-_:____
t t I
1153
2 (II =36:CRll - t+ C-A. I : _-_+----_--__-__ +L-_-_ 1 IN=61) 3 (II= la : XRl)
L_--_ @ MONTHS
___--
__&
-_-_-_t_
38 MONTHS
Fig. 5. Disease-free survival after autologous BMT. Curve I = whole autologous population. Curve 2 = first CR patients. Curve 3 = second or subsequent CR patients.
not resulted in an improved survival rate, with a higher rate of relapse and rejection (2, 7); this may be because of the lack of a “graft-versus-leukemia” effect (8) and might require an intensified preparative regimen, perhaps hyperfractionated TBI (2, 5). On the other hand, most techniques of marrow ablation associate TBI and high dose chemotherapy, and their respective timing might play a role particularly in relapse patients (4, 9). In this retrospective non-randomized study, the results are satisfying in terms of leukemic relapse and survival rate for the allogeneic non T-depleted BMT, performed in first CR, whereas there is a higher risk of relapse in Tdepleted allogeneic and in autologous BMT, performed in second or greater CR. This non-randomized study leads us to believe that an intensification of the conditioning regimen is not necessary in the first CR patients, since we did not observe too many radiation related complications with less than 5% of interstitial pneumonitis and VOD, and with a correct disease control (4-year DFS = 68.5%). Furthermore, immunosuppression of this TBI is efficient without any rejection in non T-depleted patients. This encouraged us to perform the allogeneic BMT in patients with a HLAidentical donor when possible, early in the evolution of the disease. On the other hand, results are very dismal when BMT is not performed in first CR. In this case, we have to improve the conditioning regimen without increasing the complications related to the transplantation.
REFERENCES I. Bordigoni, P.; Vernant, J. P.; Gluckman, E.; Maraninchi, D.; Milpied, N.; Fischer, A.; Lemoine, E. Benz; Jouet, J. P.; Reiffers, J. Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in first remission: a cooperative study of the Groupe d’Etude de la Greffe de Moelle Osseuse. J. Clin. Oncol. 7(6):747-753; 1989. 2. Champlain, R. E.; Ho, W. G.; Mitsuyasu, R.; Burnison, M.; Greenberg, P.; Holly, G.; Winston, D. W.; Feig, S. A.; Gale,
R. P. Graft failure and leukemia relapse following T-lymphocyte-depleted bone marrow transplants: effect of intensification of immuno-suppressive conditioning. Transplant. Proc. X1X( 1):2616-2619; 1987. R.; Gale, R. P. Bone marrow transplantation 3. Champlain, for acute leukemia: recent advances and comparison with alternative therapies. Sem. Hematol. 24( 1):55-67; 1987. H. G.; Philips, G. L. A guide to 4. Deeg, H. J.; Klingemann, bone marrow transplantation. Berlin: Springer-Verlag; 1988.
I. J. Radiation Oncology 0 Biology 0 Physics
1154
Guyotat, D.; Dutou, L.; Ehrsam, A.; Campos, I.; Archimbaud, E.; Fiere, D. Graft rejection after T-cell depleted marrow transplantation: role of fractionated irradiation. Br. J. Haematol. 65499; 1987.
Kersey, J. H.; Weisdorf, D.; Nesbit, M. E.; Lebien, T. W.; Woods, W. G.; Mac Glave, P. B.; Kim, T.; Vallera, D. A.; Goldman, A. I.; Bostrom, B.; Hurd, D.; Ramsay, N. K. C. Comparison of autologous and allogeneic bone marrow transplantation for treatment of high-risk refractory acute lymphoblastic leukemia. N. Eng. J. Med. 3 17(8):46 l-467; 1987. Mayer, R. J. chemotherapy “best choice”? Odom, L. F.;
Allogeneic transplantation versus intensive in first remission acute leukemia: is there a J. Clin. Oncol. 6( 10): 1532- 1536; 1988. August, C. S.; Githens, J. H. Remission of
November 1990, Volume 19, Number 5
relapsed leukemia during a graft versus host reaction. A “graft versus leukemia reaction” in man. Lancet 2:537-540; 1978. 9. Shank, B.; Chu, F. C.; Dinsmore, R.; Kappor, N.; Kirkpatrick, D.; Teitelbaum, H.; Reid, A.; Bonfiglio, P.; Simpson, L.; O’Reilly, R. J. Hyperfractionated total body irradiation for bone marrow transplantation. Results in 70 leukemia patients with allogeneic transplants. Int. J. Radiat. Oncol. Biol. Phys. 9: 1607- 16 11; 1983. 10. Zander, A. R.; Keating, M.; Dicke, K.; Dixon, D.; Pierce, S.; Jagannath, S.; Peters, L.; Horwitz, L.; Cockerill, K.; Spitzer, G.; Vellekoop, L.; Kantarjian, H.; Walters, R.; Mac Credie, K.; Freireich, E. J. A comparison of marrow transplantation with chemotherapy for adults with acute leukemia of poor prognosis in first complete remission. J. Clin. Oncol. 6( 10):1548-1557; 1988.
