523
WORK IN PROGRESS
Vol. 122
Total-Body Irradiation with a High-Dose-Rate Linear Accelerator for Bone-Marrow Transplantation in Aplastic Anemia and Neoplastic Disease 1
MATERIALS AND METHODS Since May 1975, 9 patients have received high-dose-rate total-body irradiation (TBI). There were 4 patients with acute myelocytic leukemia, 1 each with chronic lymphocytic leukemia, acute lymphocytic leukemia, and American Burkitt's lymphoma, and 2 with aplastic anemia, of which the last 2 had previously experienced rejection of marrow transplants administered without TBI. The recipient conditioning schedule with cytotoxic drugs is shown in TABLE I. A total dose of 750 rads to the midline was given on Day 1, using 10-MeV x rays from a Toshiba Model LMR-13 linear accelerator. Half of this dose was delivered by anteroposterior portals, the remaining half by postero-anterior portals with the patient lying on his side. The distance between the midline of the patient and the target was kept at 415 cm throughout the treatment. The overall field size at the patient midline was 124 X 124 cm. Computations of the accelerator monitor settings required to deliver the prescribed dose were based on an average of the depth doses at the midline of the head, chest (sternal notch and xiphoid levels), abdomen (umbilicus level), hip, and knee; depth dose data for a fixed target midline distance of 415 cm had been obtained previously by ion chamber measurements in a polystyrene phantom. In vivo thermoluminescence dosimetry using TLD chips confirmed the delivery of the prescribed dose to within 3 %. The dose rate at the midline of a patient of average size was about 26 rads/minute and the total treatment time was about 29 minutes. All patients were given antiemetics 30 minutes before irradiation. Bone marrow matched to histocompatibility antigens (HCA and MLC) was transplanted 24 hours later. All pre- and post-transplantation blood products were irradiated with 3,000 rads of x rays.
Tae H. Kim, M.D., John Kersey, M.D., Wilfred Sewchand, SC.D., Mark E. Nesbit, M.D., William Krivit, M.D., and Seymour H. Levitt, M.D. Nine children with various hematologic disorders underwent bone-marrow transplantation following total-body irradiation with 750 rads at a rate of 26 rads/min. from a 13-MeV linear accelerator in conjunction with cyotoxic drugs. This treatment was tolerated reasonably well, with acceptable side effects. Three patients were alive and well at 18, 11, and 7 months post-transplantation at the time this paper was written. INDEX TERMS: Anemia, aplastic • Bone marrow, transplantation. Leukemia, therapeutic radiology. Lymphoma, therapeutic radiology
Radiology 122:523-525, February 1977
Developments during the past two decades indicate that bone-marrow transplantation may be an effective treatment for certain hematopoietic and immune deficiency disorders, e.g., acute leukemia and aplastic anemia (7). Except for patients with immune deficiency disease, adequate immunosuppression is required to graft allogeneic marrow successfully. In neoplastic diseases, eradication of the malignant cells is also necessary. Total-body irradiation with a supralethal dose, cytotoxic drugs, and antilymphocyte serum are commonly used as immunosuppressive and tumor-reducing measures in many institutions (7). At the University of Minnesota, we have developed a new high-dose-rate total-body irradiation technique using 10-MeV photons from a 13-MeV linear accelerator in conjunction with cytotoxic drugs for bone-marrow transplantation. Preliminary results are described below.
Table I:
Work In Progress
University of Minnesota Marrow Transplantation Protocol
Patients with Hematologic Mal ignancy Decontamination with skin and bowel antibiotics
Day -10
-9 -8 -7 -6
A.M.
P.M.
Cytosine arabinoside, 100 mq/m ' intravenously; cyclophosphamide, 50 m q/kq intravenously (Same)
Cytosine arabinosi de (as in A.M.)
(Same)
-5
(Same)
(Same)
-4
(Same)
BCNU,* 200 mq/rn" intravenously
-3
Rest Total-body irradiation, 750 rads Marrow transplant Methotrexate, 15 mq/rn ' intravenously (with an additional 10 mq/rn ' given on days +3, +6, + 11, and weekly for 100 days
Patients with Aplastic Anemia
-11
-2
-1
o
+1
Procarbazine, 12.5 rnq/kq intravenously Antithymocyte globulins, 12 mg IgG/kg intravenously Procarbazi ne Antithymocyte globulins, white blood cells in the buffy coat
Procarbazine; cyclophospham ide, 50 mg/ kg intravenously Antithymocyte globulins, cyclophosphamide Cyclophosphamide Cyclophosphamide Total-body irradiation, 750 rad s t Marrow transplant Methotrexate, 15 mq/rn ' intravenously (with an additional 10 mq/rn ' given on days +3, +6, + 11, and weekly for 100 days)
*BCNU "" 1,3-bis-(2-chlorethyl)-1-nitrosourea. tTotal-body irradiation for aplastic anemia is given only to those whose bodies had previously rejected marrow transplants without it. Dosage is 26 rads/rninute using 10-MeV x rays.
524
WORK IN PROGRESS
Table II: Patient
Age (yr.) and Sex
J.S.
9M
0.5.
16 M
P.O.
10 F
Results of Treatment Diagnosis
Acute myelocytic leukemia
American Burkitt's lymphoma Acute myelocytic leukemia Aplastic anemia
R.B.
6F
R.O.
14 M
Acute myelocytic leukemia
K.A.
16 F
Aplastic anemia
E.F.
17 M
Chronic Iymphocytic leukemia
M.W.
16 F
Acute lymphocytic leukemia
E.K.
6M
Acute myelocytic leukemia
Outcome Mild graft versus host disease; al ive at 18 months* in remission; pericardial effusion Alive at 11 months; doing well
Pneumocystis carinii infection; died in 120 days Chronic graft versus host disease; staphylococcal pneumonia; died in 100 days Relapse of disease on 50th day; died in 60 days Subdural hematoma, probably due to trauma; died in 20 days Gastrointestinal bleed ing associated with appendiceal abscess and graft versus host disease; died in 40 days Gram-negative sepsis; died in 20 days Rem issi on at 7 months; doing well
*Survival time is calculated from the day of marrow transplantation.
RESULTS (TABLE II) All patients tolerated irradiation well except for 3 patients who began vomiting at the end of the treatment. All patients exhibited minimal to moderate gastrointestinal symptoms lasting about 1-2 weeks or less, including nausea, vomiting, and diarrhea, during or immediately after irradiation. None of these symptoms were life-threatening with adequate supportive treatment. One patient had gastrointestinal bleeding associated with an appendiceal abscess and biopsy-proved graft versus host disease on the 35th post-transplantation day and subsequently died. All patients had mild skin erythema and swelling of the parotid gland which subsided without specific treatment. Six patients had fever ranging from 38.3 to 40 0 C (101 0 to 104 0 F) immediately after irradiation and lasting for 12 hours to 4 days. Five of 9 patients have experienced episodes of focal or generalized infiltrative change as seen on chest radiographs during their post-transplantation course. One of them was found to have Pneumocystis carinii infection on biopsy, while 3 had various bacterial infections. The fifth patient had a generalized infiltrate of the lung with negative culture on the 66th posttransplantation day. Radiographic changes disappeared on the 120th post-transplantation day, and he was still doing well at 11 months. Three of the 6 patients who died had severe pulmonary infection in addition to the cause of death (graft vs. host disease, bleeding, and sepsis, respectively). One patient was still alive 18 months after treatment without
February 1977
evidence of disease but demonstrated moderate pericardial effusion 4 months after transplantation. One patient with acute myelocytic leukemia had recurrence of disease on the 50th post-transplantation day and subsequently died. At the time this paper was written, 3 of the 9 patients treated were still living at 18, 11, and 7 months, respectively. DISCUSSION Since the first successful human allogeneic bone-marrow transplant in 1958 for radiation accident victims (6), an increasing number of patients with otherwise fatal hematopoietic disorders have been treated with supralethal-dose total-body irradiation followed by syngeneic or allogeneic bone-marrow transplantation (2, 6, 7). Early results were dismal, but survival has improved steadily with better knowledge of immunology, development of histocompatability testing methods, and the recent addition of cytotoxic drugs (7) to total-body irradiation for the conditioning of recipients. Various dose regimens have been tested to obtain maximum tumoricidal and immunosuppressive effects while avoiding fatal complications of high-dose irradiation (2, 4, 6, 7). The Seattle group has shown the most encouraging results by conditioning recipients with cytotoxic drugs and 1,000 rads total dose, delivered at a rate of 5.0-5.7 R/minute in air using two opposing 60CO sources (1). We used a similar method for a few of our patients but found that it presented a number of problems in practical application for two reasons. For one thing, a treatment time of 4 hours or more is required, depending on the condition of the patient. This created serious problems not only for the patients but also for all personnel involved in their care. In most instances, the recipients were in very poor clinical condition both from their disease and from conditioning with chemotherapy. It was very difficult for them to lie in one position without moving for such a long period of time. Furthermore, many patients demonstrated gastrointestinal symptoms during irradiation, meaning that treatment had to be interrupted several times and total treatment time was prolonged. In addition, the fact that the treatment machine was occupied by one patient for such a long time disrupted the treatment of regular patients. We were able to overcome these problems by shortening the total treatment time to less than 30 minutes with 10-MeV x rays at a rate of 26 R/minute. The choice of a total dose of 750 rads was based on our previous study with experimental animals, comparing the RBE of 10-MeV x rays at a rate of 35 rads/minute to that of 60Co gamma rays at a rate of 6 rads/minute (3), which showed that 750 rads of 10-MeV x rays delivered at this rate were equivalent to 1,000 rads of 60Cogamma rays delivered at a rate of 5 rads/ minute. Simultaneous irradiation by two opposing sources is the best method of irradiating the patient homogeneously, but the necessary equipment is not available at most medical centers. However, we feel that we can minimize the heterogeneity of dose distribution by using a high-energy beam and a longer target-midplane distance. Our calculations, which were confirmed by TLD dosimetry, showed that the dose difference between the anterior and posterior chest wall after the first half of treatment through an anteroposterior portal was on the order of 25 % for an average AP thickness of 18 cm. This difference is fully compensated for by the second half of treatment from the opposing portal, which is completed 15 minutes later. Tolerance of treatment has been satisfactory. Gastrointestinal
Vol. 122
525
WORK IN PROGRESS
symptoms have not been a serious problem, and we have no evidence that total-body irradiation with high-dose-rate x rays has increased the incidence of pulmonary infection. Pericardial effusion is a fairly common late effect when a large dose of radiation is administered to the heart (5). The pericardial effusion sometimes seen after mantle-field irradiation for Hodgkin's disease using a dose of 4,000 rads in 4 weeks usually disappears without specific treatment. The long-term effects of the pericardial effusion seen in patients receiving 750 rads of total-body irradiation have not yet been assessed. The number of patients treated in this manner is small, and we do not know the long-term side effects due to limited follow-up time. However, our preliminary results seem to indicate that high-dose-rate total-body irradiation with a total dose of 750 rads gives good therapeutic results with less patient discomfort.
ADDENDUM: Since this paper was submitted, 3 additional patients have undergone bone-marrow transplantation. Two patients with acute myelocytic leukemia are alive and well at 5 months and 1 month, respectively; the third patient, who had American Burkitt's lymphoma, died within 1 month from persistent disease.
Work In Progress
REFERENCES 1. Buckner CD, Clift RA, Fefer A, et al: Human marrow transplantation-current status. Progr Hematol 8:299-324, 1973 2. Cline MJ, Gale RP, Stiehm ER, et al: Bone marrow transplantation in man. Ann Intern Med 83:691-708, Nov 1975 3. Feola JM, Song CW, Khan FM, et al: lethal response of C57Bl mice to 10 MeV x-rays and to GOCo gamma-rays. Int J Radiat Bioi 26: 161-165, Aug 1974 4. Gengozian N, Edwards Cl, Vodopick HA, et al: Bone marrow transplantation in a leukemic patient following immunosuppression with antithymocyte globulin and total body irradiation. Transplantation 15: 446-454, May 1973 5. Kagan AR, Hafermann M, Hamilton M, et al: Etiology, diagnosis and management of pericardial effusion after irradiation. Radiol Clin Bioi 41:171-182, 1972 6. Mathe G, Schwarzenberg l: Bone-marrow transplantation in France. 1958-1973. Transplant Proc 6:335-343, Dec 1974 7. Thomas ED, Storb R, Clift RA, et al: Bone-marrow transplantation. N Engl J Med 292:832-843, 17 Apr 1975; 895-902, 24 Apr 1975 1 From the Departments of Therapeutic Radiology (T.H.K., Box 494 Mayo; W.S.,S.H.L.) and Pediatrics, (J.K.,M.E.N.,W.K.) University of Minnesota Hospitals, Minneapolis, Minn. 55455. Presented at the Work In Progress: Radiation Therapy session of the Sixty-second Scientific Assembly and Annual Meeting of the Radiological Society of North America, Chicago, III., Nov. 14-19, 1976. Supported by research grants CA 15548 and CA 16545 from the National Cancer Institute.
WORK IN PROGRESS
Vol. 122
Total-Body Irradiation with a High-Dose-Rate Linear Accelerator for Bone-Marrow Transplantation in Aplastic Anemia and Neoplastic Disease 1
MATERIALS AND METHODS Since May 1975, 9 patients have received high-dose-rate total-body irradiation (TBI). There were 4 patients with acute myelocytic leukemia, 1 each with chronic lymphocytic leukemia, acute lymphocytic leukemia, and American Burkitt's lymphoma, and 2 with aplastic anemia, of which the last 2 had previously experienced rejection of marrow transplants administered without TBI. The recipient conditioning schedule with cytotoxic drugs is shown in TABLE I. A total dose of 750 rads to the midline was given on Day 1, using 10-MeV x rays from a Toshiba Model LMR-13 linear accelerator. Half of this dose was delivered by anteroposterior portals, the remaining half by postero-anterior portals with the patient lying on his side. The distance between the midline of the patient and the target was kept at 415 cm throughout the treatment. The overall field size at the patient midline was 124 X 124 cm. Computations of the accelerator monitor settings required to deliver the prescribed dose were based on an average of the depth doses at the midline of the head, chest (sternal notch and xiphoid levels), abdomen (umbilicus level), hip, and knee; depth dose data for a fixed target midline distance of 415 cm had been obtained previously by ion chamber measurements in a polystyrene phantom. In vivo thermoluminescence dosimetry using TLD chips confirmed the delivery of the prescribed dose to within 3 %. The dose rate at the midline of a patient of average size was about 26 rads/minute and the total treatment time was about 29 minutes. All patients were given antiemetics 30 minutes before irradiation. Bone marrow matched to histocompatibility antigens (HCA and MLC) was transplanted 24 hours later. All pre- and post-transplantation blood products were irradiated with 3,000 rads of x rays.
Tae H. Kim, M.D., John Kersey, M.D., Wilfred Sewchand, SC.D., Mark E. Nesbit, M.D., William Krivit, M.D., and Seymour H. Levitt, M.D. Nine children with various hematologic disorders underwent bone-marrow transplantation following total-body irradiation with 750 rads at a rate of 26 rads/min. from a 13-MeV linear accelerator in conjunction with cyotoxic drugs. This treatment was tolerated reasonably well, with acceptable side effects. Three patients were alive and well at 18, 11, and 7 months post-transplantation at the time this paper was written. INDEX TERMS: Anemia, aplastic • Bone marrow, transplantation. Leukemia, therapeutic radiology. Lymphoma, therapeutic radiology
Radiology 122:523-525, February 1977
Developments during the past two decades indicate that bone-marrow transplantation may be an effective treatment for certain hematopoietic and immune deficiency disorders, e.g., acute leukemia and aplastic anemia (7). Except for patients with immune deficiency disease, adequate immunosuppression is required to graft allogeneic marrow successfully. In neoplastic diseases, eradication of the malignant cells is also necessary. Total-body irradiation with a supralethal dose, cytotoxic drugs, and antilymphocyte serum are commonly used as immunosuppressive and tumor-reducing measures in many institutions (7). At the University of Minnesota, we have developed a new high-dose-rate total-body irradiation technique using 10-MeV photons from a 13-MeV linear accelerator in conjunction with cytotoxic drugs for bone-marrow transplantation. Preliminary results are described below.
Table I:
Work In Progress
University of Minnesota Marrow Transplantation Protocol
Patients with Hematologic Mal ignancy Decontamination with skin and bowel antibiotics
Day -10
-9 -8 -7 -6
A.M.
P.M.
Cytosine arabinoside, 100 mq/m ' intravenously; cyclophosphamide, 50 m q/kq intravenously (Same)
Cytosine arabinosi de (as in A.M.)
(Same)
-5
(Same)
(Same)
-4
(Same)
BCNU,* 200 mq/rn" intravenously
-3
Rest Total-body irradiation, 750 rads Marrow transplant Methotrexate, 15 mq/rn ' intravenously (with an additional 10 mq/rn ' given on days +3, +6, + 11, and weekly for 100 days
Patients with Aplastic Anemia
-11
-2
-1
o
+1
Procarbazine, 12.5 rnq/kq intravenously Antithymocyte globulins, 12 mg IgG/kg intravenously Procarbazi ne Antithymocyte globulins, white blood cells in the buffy coat
Procarbazine; cyclophospham ide, 50 mg/ kg intravenously Antithymocyte globulins, cyclophosphamide Cyclophosphamide Cyclophosphamide Total-body irradiation, 750 rad s t Marrow transplant Methotrexate, 15 mq/rn ' intravenously (with an additional 10 mq/rn ' given on days +3, +6, + 11, and weekly for 100 days)
*BCNU "" 1,3-bis-(2-chlorethyl)-1-nitrosourea. tTotal-body irradiation for aplastic anemia is given only to those whose bodies had previously rejected marrow transplants without it. Dosage is 26 rads/rninute using 10-MeV x rays.
524
WORK IN PROGRESS
Table II: Patient
Age (yr.) and Sex
J.S.
9M
0.5.
16 M
P.O.
10 F
Results of Treatment Diagnosis
Acute myelocytic leukemia
American Burkitt's lymphoma Acute myelocytic leukemia Aplastic anemia
R.B.
6F
R.O.
14 M
Acute myelocytic leukemia
K.A.
16 F
Aplastic anemia
E.F.
17 M
Chronic Iymphocytic leukemia
M.W.
16 F
Acute lymphocytic leukemia
E.K.
6M
Acute myelocytic leukemia
Outcome Mild graft versus host disease; al ive at 18 months* in remission; pericardial effusion Alive at 11 months; doing well
Pneumocystis carinii infection; died in 120 days Chronic graft versus host disease; staphylococcal pneumonia; died in 100 days Relapse of disease on 50th day; died in 60 days Subdural hematoma, probably due to trauma; died in 20 days Gastrointestinal bleed ing associated with appendiceal abscess and graft versus host disease; died in 40 days Gram-negative sepsis; died in 20 days Rem issi on at 7 months; doing well
*Survival time is calculated from the day of marrow transplantation.
RESULTS (TABLE II) All patients tolerated irradiation well except for 3 patients who began vomiting at the end of the treatment. All patients exhibited minimal to moderate gastrointestinal symptoms lasting about 1-2 weeks or less, including nausea, vomiting, and diarrhea, during or immediately after irradiation. None of these symptoms were life-threatening with adequate supportive treatment. One patient had gastrointestinal bleeding associated with an appendiceal abscess and biopsy-proved graft versus host disease on the 35th post-transplantation day and subsequently died. All patients had mild skin erythema and swelling of the parotid gland which subsided without specific treatment. Six patients had fever ranging from 38.3 to 40 0 C (101 0 to 104 0 F) immediately after irradiation and lasting for 12 hours to 4 days. Five of 9 patients have experienced episodes of focal or generalized infiltrative change as seen on chest radiographs during their post-transplantation course. One of them was found to have Pneumocystis carinii infection on biopsy, while 3 had various bacterial infections. The fifth patient had a generalized infiltrate of the lung with negative culture on the 66th posttransplantation day. Radiographic changes disappeared on the 120th post-transplantation day, and he was still doing well at 11 months. Three of the 6 patients who died had severe pulmonary infection in addition to the cause of death (graft vs. host disease, bleeding, and sepsis, respectively). One patient was still alive 18 months after treatment without
February 1977
evidence of disease but demonstrated moderate pericardial effusion 4 months after transplantation. One patient with acute myelocytic leukemia had recurrence of disease on the 50th post-transplantation day and subsequently died. At the time this paper was written, 3 of the 9 patients treated were still living at 18, 11, and 7 months, respectively. DISCUSSION Since the first successful human allogeneic bone-marrow transplant in 1958 for radiation accident victims (6), an increasing number of patients with otherwise fatal hematopoietic disorders have been treated with supralethal-dose total-body irradiation followed by syngeneic or allogeneic bone-marrow transplantation (2, 6, 7). Early results were dismal, but survival has improved steadily with better knowledge of immunology, development of histocompatability testing methods, and the recent addition of cytotoxic drugs (7) to total-body irradiation for the conditioning of recipients. Various dose regimens have been tested to obtain maximum tumoricidal and immunosuppressive effects while avoiding fatal complications of high-dose irradiation (2, 4, 6, 7). The Seattle group has shown the most encouraging results by conditioning recipients with cytotoxic drugs and 1,000 rads total dose, delivered at a rate of 5.0-5.7 R/minute in air using two opposing 60CO sources (1). We used a similar method for a few of our patients but found that it presented a number of problems in practical application for two reasons. For one thing, a treatment time of 4 hours or more is required, depending on the condition of the patient. This created serious problems not only for the patients but also for all personnel involved in their care. In most instances, the recipients were in very poor clinical condition both from their disease and from conditioning with chemotherapy. It was very difficult for them to lie in one position without moving for such a long period of time. Furthermore, many patients demonstrated gastrointestinal symptoms during irradiation, meaning that treatment had to be interrupted several times and total treatment time was prolonged. In addition, the fact that the treatment machine was occupied by one patient for such a long time disrupted the treatment of regular patients. We were able to overcome these problems by shortening the total treatment time to less than 30 minutes with 10-MeV x rays at a rate of 26 R/minute. The choice of a total dose of 750 rads was based on our previous study with experimental animals, comparing the RBE of 10-MeV x rays at a rate of 35 rads/minute to that of 60Co gamma rays at a rate of 6 rads/minute (3), which showed that 750 rads of 10-MeV x rays delivered at this rate were equivalent to 1,000 rads of 60Cogamma rays delivered at a rate of 5 rads/ minute. Simultaneous irradiation by two opposing sources is the best method of irradiating the patient homogeneously, but the necessary equipment is not available at most medical centers. However, we feel that we can minimize the heterogeneity of dose distribution by using a high-energy beam and a longer target-midplane distance. Our calculations, which were confirmed by TLD dosimetry, showed that the dose difference between the anterior and posterior chest wall after the first half of treatment through an anteroposterior portal was on the order of 25 % for an average AP thickness of 18 cm. This difference is fully compensated for by the second half of treatment from the opposing portal, which is completed 15 minutes later. Tolerance of treatment has been satisfactory. Gastrointestinal
Vol. 122
525
WORK IN PROGRESS
symptoms have not been a serious problem, and we have no evidence that total-body irradiation with high-dose-rate x rays has increased the incidence of pulmonary infection. Pericardial effusion is a fairly common late effect when a large dose of radiation is administered to the heart (5). The pericardial effusion sometimes seen after mantle-field irradiation for Hodgkin's disease using a dose of 4,000 rads in 4 weeks usually disappears without specific treatment. The long-term effects of the pericardial effusion seen in patients receiving 750 rads of total-body irradiation have not yet been assessed. The number of patients treated in this manner is small, and we do not know the long-term side effects due to limited follow-up time. However, our preliminary results seem to indicate that high-dose-rate total-body irradiation with a total dose of 750 rads gives good therapeutic results with less patient discomfort.
ADDENDUM: Since this paper was submitted, 3 additional patients have undergone bone-marrow transplantation. Two patients with acute myelocytic leukemia are alive and well at 5 months and 1 month, respectively; the third patient, who had American Burkitt's lymphoma, died within 1 month from persistent disease.
Work In Progress
REFERENCES 1. Buckner CD, Clift RA, Fefer A, et al: Human marrow transplantation-current status. Progr Hematol 8:299-324, 1973 2. Cline MJ, Gale RP, Stiehm ER, et al: Bone marrow transplantation in man. Ann Intern Med 83:691-708, Nov 1975 3. Feola JM, Song CW, Khan FM, et al: lethal response of C57Bl mice to 10 MeV x-rays and to GOCo gamma-rays. Int J Radiat Bioi 26: 161-165, Aug 1974 4. Gengozian N, Edwards Cl, Vodopick HA, et al: Bone marrow transplantation in a leukemic patient following immunosuppression with antithymocyte globulin and total body irradiation. Transplantation 15: 446-454, May 1973 5. Kagan AR, Hafermann M, Hamilton M, et al: Etiology, diagnosis and management of pericardial effusion after irradiation. Radiol Clin Bioi 41:171-182, 1972 6. Mathe G, Schwarzenberg l: Bone-marrow transplantation in France. 1958-1973. Transplant Proc 6:335-343, Dec 1974 7. Thomas ED, Storb R, Clift RA, et al: Bone-marrow transplantation. N Engl J Med 292:832-843, 17 Apr 1975; 895-902, 24 Apr 1975 1 From the Departments of Therapeutic Radiology (T.H.K., Box 494 Mayo; W.S.,S.H.L.) and Pediatrics, (J.K.,M.E.N.,W.K.) University of Minnesota Hospitals, Minneapolis, Minn. 55455. Presented at the Work In Progress: Radiation Therapy session of the Sixty-second Scientific Assembly and Annual Meeting of the Radiological Society of North America, Chicago, III., Nov. 14-19, 1976. Supported by research grants CA 15548 and CA 16545 from the National Cancer Institute.
