scholarly journals Cyclosporin-A abrogates transfusion-induced sensitization and prevents marrow graft rejection in DLA-identical canine littermates

Blood ◽  
1982 ◽  
Vol 60 (2) ◽  
pp. 524-526
Author(s):  
R Storb ◽  
HJ Deeg ◽  
K Atkinson ◽  
PL Weiden ◽  
G Sale ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
Total Body Irradiation ◽  
Whole Blood ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Immunosuppressive Agent ◽  
Blood Transfusions ◽  
Marrow Graft ◽  
Short Course ◽  
Total Body

Previous studies had shown that marrow graft rejection generally did not occur in untransfused dogs given 900-rad total body irradiation and hemopoietic grafts from DLA identical littermates (only 1 of 59 rejected), but was seen in all instances after three preceding transfusions of whole blood from the marrow donor on days -24, -17, and -10 before transplantation (19 of 19 rejected). The present study was undertaken to investigate whether immunization by 3 preceding transfusions of whole blood from the DLA-identical littermate marrow donor could be abrogated by administration of the immunosuppressive agent cyclo-sporin-A, 20 mg/kg/day intramuscularly on days -5 to 0. Seven of 10 dogs showed sustained marrow engraftment. 2 failed to engraft, and 1 dog died to early to be evaluated. It was concluded that immunization to non-DLA antigens by preceding whole blood transfusions could be abrogated in most cases by a short-course of cyclosporin-A before total body irradiation and marrow transplantation, resulting in successful and sustained marrow engraftment.

scholarly journals Cyclosporin-A abrogates transfusion-induced sensitization and prevents marrow graft rejection in DLA-identical canine littermates

Blood ◽  
1982 ◽  
Vol 60 (2) ◽  
pp. 524-526 ◽  
Author(s):  
R Storb ◽  
HJ Deeg ◽  
K Atkinson ◽  
PL Weiden ◽  
G Sale ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
Total Body Irradiation ◽  
Whole Blood ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Immunosuppressive Agent ◽  
Blood Transfusions ◽  
Marrow Graft ◽  
Short Course ◽  
Total Body

Abstract Previous studies had shown that marrow graft rejection generally did not occur in untransfused dogs given 900-rad total body irradiation and hemopoietic grafts from DLA identical littermates (only 1 of 59 rejected), but was seen in all instances after three preceding transfusions of whole blood from the marrow donor on days -24, -17, and -10 before transplantation (19 of 19 rejected). The present study was undertaken to investigate whether immunization by 3 preceding transfusions of whole blood from the DLA-identical littermate marrow donor could be abrogated by administration of the immunosuppressive agent cyclo-sporin-A, 20 mg/kg/day intramuscularly on days -5 to 0. Seven of 10 dogs showed sustained marrow engraftment. 2 failed to engraft, and 1 dog died to early to be evaluated. It was concluded that immunization to non-DLA antigens by preceding whole blood transfusions could be abrogated in most cases by a short-course of cyclosporin-A before total body irradiation and marrow transplantation, resulting in successful and sustained marrow engraftment.

scholarly journals Aplastic anemia treated by allogeneic bone marrow transplantation: a report on 49 new cases from Seattle

Blood ◽  
1976 ◽  
Vol 48 (6) ◽  
pp. 817-841 ◽  
Author(s):  
R Storb ◽  
ED Thomas ◽  
PL Weiden ◽  
CD Buckner ◽  
RA Clift ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Fungal Infections ◽  
Allogeneic Bone Marrow Transplantation ◽  
Severe Aplastic Anemia ◽  
Allogeneic Bone ◽  
Marrow Graft ◽  
Term Survival ◽  
Total Body

Forty-nine patients with severe aplastic anemia, 33 due to unknown cause, 11 drug or chemical related, 2 associated with hepatitis, 1 with paroxysmal nocturnal hemoglobinuria, and 2 possibly associated with Fanconi syndrome did not show recovery after 0.5–96 (median 2) mo of conventional therapy. Twenty-two were infected and 21 were refractory to random platelet transfusions at the time of admission. All were given marrow grafts from HLA-identical siblings. Forty-five were conditioned for grafting by cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and four by 1000 rad total body irradiation. All were given intermittent methotrexate therapy within the first 100 days of grafting to modify graft-versus-host disease (GVHD). Three patients died from infection too early to evaluate (days 1–8). Forty-six had marrow engraftment. Of these, 20 are surviving with good peripheral blood counts between 186 and 999 days, and 18 have returned to normal activities. Chronic GCHD is a problem in five. Twelve patients died of infection following rejection of the marrow graft. Twelve patients died with bacterial or fungal infections or interstitial pneumonia and active GVHD or soon following resolution of GVHD. Two patients died with marrow engraftment and no GVHD, one with an interstitial, and the other with a bacterial pneumonia. Thirty-six patients who had received random donor blood transfusions were randomly assigned to receive either CY or procarbazine-antithymocyte globulin-CY as conditioning regimens to test whether the incidence of graft rejection could be decreased. There was no difference in the incidence of graft rejection between the two regimens. In 13 patients with rejection, second transplants were attempted either with the original marrow donor (9 patients) or another HLA-identical sibling (4 patients). Three of these transplants were not evaluable, seven were unsuccessful and three were successful with only one of the three surviving for more than 468 days. In conclusion, the long-term survival of 41% of the patients in the present study is similar to that achieved in our first 24 patients, and confirms the importance of marrow transplantation for the treatment of severe aplastic anemia. Marrow graft rejection, GVHD, and infections continue to be the major causes of failure.

scholarly journals Prevention of graft rejection following bone marrow transplantation

Blood ◽  
1981 ◽  
Vol 57 (1) ◽  
pp. 9-12
Author(s):  
RP Gale ◽  
W Ho ◽  
S Feig ◽  
R Champlin ◽  
A Tesler ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Total Body Irradiation ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Low Dose ◽  
Conditioning Regimen ◽  
Actuarial Survival ◽  
Total Body

Bone marrow transplantation from an HLA-identical sibling is increasingly used in the treatment of severe aplastic anemia. One major problem with this approach is graft rejection that occurs in 25%-60% of patients conditioned for transplantation with cyclophosphamide. At most transplant centers it has been difficult to accurately identify patients at high risk for graft rejection. We studied a conditioning regimen of cyclophosphamide (200 mg per kg) and low-dose total body irradiation (3 Gy; equivalent to 300 rad) in 23 consecutive unselected patients with aplastic anemia followed for a minimum of 6 mo. There was only one episode of graft rejection. Graft-versus-host disease and interstitial pneumonitis were not increased by the more intensive conditioning regimen. Actuarial survival was 61% at 1 yr and 49% at 2.5 yr. Cyclophosphamide and low-dose total body irradiation is an effective conditioning regimen in patients with aplastic anemia. It may be particularly useful when accurate predictive tests of graft rejection are not available as is the case in most transplant centers.

scholarly journals Comparison of fractionated to single-dose total body irradiation in conditioning canine littermates for DLA-identical marrow grafts

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 1139-1143 ◽  
Author(s):  
R Storb ◽  
RF Raff ◽  
FR Appelbaum ◽  
TC Graham ◽  
FG Schuening ◽  
...  
Keyword(s):  
Single Dose ◽  
T Cell ◽  
Total Body Irradiation ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Clinical Transplantation ◽  
Reported Study ◽  
Total Body ◽  
Lethal Doses ◽  
Conditioning Programs

Abstract We explored the ability of fractionated total body irradiation (TBI) given at a rate of 7 cGy/min from opposing dual 60Co sources at otherwise lethal doses of 450, 600, 700, 800, and 920 cGy to condition dogs for marrow grafts from DLA-identical littermates. Results were compared with those of a previously reported study using single-dose TBI administered under otherwise identical conditions. Fractionated TBI was less immunosuppressive than single-dose TBI, as evidenced by a significantly higher rate of graft rejection (P = .001). Specifically, sustained allogeneic engraftment was observed in only two of 18 (11%) dogs that received 600 to 800 cGy fractionated TBI as compared with 11 of 17 (65%) dogs that received comparable doses of single-dose TBI. Only at 450 cGy (none of the ten dogs studied had sustained engraftment) and at 920 cGy (four of five dogs that received fractionated and 20 of 21 dogs that received single-dose TBI engrafted) were we unable to find differences between the two modes of radiation. Most dogs that rejected their graft survived with autologous recovery (13 of 22 that received fractionated and eight of 12 that received single-dose TBI; P = .49), presumably the result of extended support provided by the transient allogeneic grafts. We conclude that at equivalent doses fractionated TBI is significantly less effective than single-dose TBI to condition DLA-identical littermate dogs for marrow transplantation. These findings have implications for the design of conditioning programs in clinical transplantation, especially when T- cell-depleted marrow grafts are used.

scholarly journals One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation

Blood ◽  
1977 ◽  
Vol 49 (4) ◽  
pp. 511-533 ◽  
Author(s):  
ED Thomas ◽  
CD Buckner ◽  
M Banaji ◽  
RA Clift ◽  
A Fefer ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Interstitial Pneumonia ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Etiologic Agent ◽  
Myelogenous Leukemia ◽  
Survival Times ◽  
Marrow Graft ◽  
Total Body

Abstract One hundred patients, 54 with acute myelogenous leukemia (AML) and 46 with acute lymphoblastic leukemia (ALL), considered to be in the end stages of their disease, after combination chemotherapy were treated by marrow transplantation. All patients were given a marrow graft from an HLA-identical sibling after receiving 1000-rad total body irradiation (TBI). One group of 43 patients was given cyclophosphamide (CY), 60 mg/kg on each of 2 days, 5 and 4 days before TBI. In a second group of 31 patients, additional chemotherapy was given before CY and TBI. In a third group of 19 patients, BCNU was given before CY and TBI. A fourth group of 7 patients received other chemotherapy regimens before TBI. Six patients died 3–17 days after marrow infusion without evidence of engraftment. Ninety-four patients were engrafted and only one patient rejected the graft. Thirteen patients are alive with a marrow graft, on no maintenance antileukemic therapy, and without recurrent leukemia 1–4 1/2 yr after transplantation. Three have chronic graft-versus-host disease (GVHD). Four patients are alive 1 1/2 - 3 1/2 yr after grafting but have had a relapse of their leukemia. Of 93 evaluable patients, 19 did not develop GVHD and 24 developed very mild GVHD. Fifty patients developed moderate to severe GVHD, and 40 of these were treated with antithymocyte globulin. Interstitial pneumonia occurred in 54 patients and was the primary cause of death in 34. Interstitial pneumonia often occurred in association with GVHD and the most common etiologic agent was cytomegalovirus. A total of 31 patients have had a relapse of leukemia. There was no definite correlation between relapse of leukemia and the presence or absence of GVHD. The relapse rate appeared to be relatively constant over the first 2 yr and was extremely low after that time. Neither survival nor leukemic relapse appeared to be influenced by the type of leukemia nor by the preparative chemotherapy regimen given before TBI. Patients in fair clinical condition at the time of transplantation showed significantly longer survival times than patients in poor condition (p = 0.001). This observation, coupled with the observation that some patients may be cured of their disease, indicates that marrow transplantation should now be undertaken earlier in the management of patients with acute leukemia who have an HLA- matched sibling marrow donor.

scholarly journals Aplastic anemia treated by allogeneic bone marrow transplantation: a report on 49 new cases from Seattle

Blood ◽  
1976 ◽  
Vol 48 (6) ◽  
pp. 817-841 ◽  
Author(s):  
R Storb ◽  
ED Thomas ◽  
PL Weiden ◽  
CD Buckner ◽  
RA Clift ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Fungal Infections ◽  
Allogeneic Bone Marrow Transplantation ◽  
Severe Aplastic Anemia ◽  
Allogeneic Bone ◽  
Marrow Graft ◽  
Term Survival ◽  
Total Body

Abstract Forty-nine patients with severe aplastic anemia, 33 due to unknown cause, 11 drug or chemical related, 2 associated with hepatitis, 1 with paroxysmal nocturnal hemoglobinuria, and 2 possibly associated with Fanconi syndrome did not show recovery after 0.5–96 (median 2) mo of conventional therapy. Twenty-two were infected and 21 were refractory to random platelet transfusions at the time of admission. All were given marrow grafts from HLA-identical siblings. Forty-five were conditioned for grafting by cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and four by 1000 rad total body irradiation. All were given intermittent methotrexate therapy within the first 100 days of grafting to modify graft-versus-host disease (GVHD). Three patients died from infection too early to evaluate (days 1–8). Forty-six had marrow engraftment. Of these, 20 are surviving with good peripheral blood counts between 186 and 999 days, and 18 have returned to normal activities. Chronic GCHD is a problem in five. Twelve patients died of infection following rejection of the marrow graft. Twelve patients died with bacterial or fungal infections or interstitial pneumonia and active GVHD or soon following resolution of GVHD. Two patients died with marrow engraftment and no GVHD, one with an interstitial, and the other with a bacterial pneumonia. Thirty-six patients who had received random donor blood transfusions were randomly assigned to receive either CY or procarbazine-antithymocyte globulin-CY as conditioning regimens to test whether the incidence of graft rejection could be decreased. There was no difference in the incidence of graft rejection between the two regimens. In 13 patients with rejection, second transplants were attempted either with the original marrow donor (9 patients) or another HLA-identical sibling (4 patients). Three of these transplants were not evaluable, seven were unsuccessful and three were successful with only one of the three surviving for more than 468 days. In conclusion, the long-term survival of 41% of the patients in the present study is similar to that achieved in our first 24 patients, and confirms the importance of marrow transplantation for the treatment of severe aplastic anemia. Marrow graft rejection, GVHD, and infections continue to be the major causes of failure.

scholarly journals Comparison of fractionated to single-dose total body irradiation in conditioning canine littermates for DLA-identical marrow grafts

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 1139-1143 ◽  
Author(s):  
R Storb ◽  
RF Raff ◽  
FR Appelbaum ◽  
TC Graham ◽  
FG Schuening ◽  
...  
Keyword(s):  
Single Dose ◽  
T Cell ◽  
Total Body Irradiation ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Clinical Transplantation ◽  
Reported Study ◽  
Total Body ◽  
Lethal Doses ◽  
Conditioning Programs

We explored the ability of fractionated total body irradiation (TBI) given at a rate of 7 cGy/min from opposing dual 60Co sources at otherwise lethal doses of 450, 600, 700, 800, and 920 cGy to condition dogs for marrow grafts from DLA-identical littermates. Results were compared with those of a previously reported study using single-dose TBI administered under otherwise identical conditions. Fractionated TBI was less immunosuppressive than single-dose TBI, as evidenced by a significantly higher rate of graft rejection (P = .001). Specifically, sustained allogeneic engraftment was observed in only two of 18 (11%) dogs that received 600 to 800 cGy fractionated TBI as compared with 11 of 17 (65%) dogs that received comparable doses of single-dose TBI. Only at 450 cGy (none of the ten dogs studied had sustained engraftment) and at 920 cGy (four of five dogs that received fractionated and 20 of 21 dogs that received single-dose TBI engrafted) were we unable to find differences between the two modes of radiation. Most dogs that rejected their graft survived with autologous recovery (13 of 22 that received fractionated and eight of 12 that received single-dose TBI; P = .49), presumably the result of extended support provided by the transient allogeneic grafts. We conclude that at equivalent doses fractionated TBI is significantly less effective than single-dose TBI to condition DLA-identical littermate dogs for marrow transplantation. These findings have implications for the design of conditioning programs in clinical transplantation, especially when T- cell-depleted marrow grafts are used.

scholarly journals The Effect of Preceding Blood Transfusions on the Fate of Homologous Bone Marrow Grafts in Lethally Irradiated Monkeys

Blood ◽  
1967 ◽  
Vol 30 (6) ◽  
pp. 749-757 ◽  
Author(s):  
L. M. VAN PUTTEN ◽  
D. W. VAN BEKKUM ◽  
M. J. DE VRIES ◽  
H. BALNEB
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Rhesus Monkeys ◽  
Third Party ◽  
Blood Transfusions ◽  
Bone Marrow Transplants ◽  
Multiple Blood ◽  
Total Body

Abstract Attempts at bone marrow transplantation after total body irradiation in Rhesus monkeys which have received multiple blood transfusions leads only rarely to acceptance of the graft, whereas in animals that were not previously transfused, a take of the graft is the rule. Immunization against subsequent bone marrow transplants was not only observed after transfusions with blood from the future donor, but also after multiple transfusions from unrelated third-party donors. From these observations in monkeys it is concluded that many of the failures to observe a take of attempted bone marrow transplants in man may be related to the fact that the recipient had received multiple blood transfusions prior to transplantation.

scholarly journals Prevention of graft rejection following bone marrow transplantation

Blood ◽  
1981 ◽  
Vol 57 (1) ◽  
pp. 9-12 ◽  
Author(s):  
RP Gale ◽  
W Ho ◽  
S Feig ◽  
R Champlin ◽  
A Tesler ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Total Body Irradiation ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Low Dose ◽  
Conditioning Regimen ◽  
Actuarial Survival ◽  
Total Body

Abstract Bone marrow transplantation from an HLA-identical sibling is increasingly used in the treatment of severe aplastic anemia. One major problem with this approach is graft rejection that occurs in 25%-60% of patients conditioned for transplantation with cyclophosphamide. At most transplant centers it has been difficult to accurately identify patients at high risk for graft rejection. We studied a conditioning regimen of cyclophosphamide (200 mg per kg) and low-dose total body irradiation (3 Gy; equivalent to 300 rad) in 23 consecutive unselected patients with aplastic anemia followed for a minimum of 6 mo. There was only one episode of graft rejection. Graft-versus-host disease and interstitial pneumonitis were not increased by the more intensive conditioning regimen. Actuarial survival was 61% at 1 yr and 49% at 2.5 yr. Cyclophosphamide and low-dose total body irradiation is an effective conditioning regimen in patients with aplastic anemia. It may be particularly useful when accurate predictive tests of graft rejection are not available as is the case in most transplant centers.

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