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Allogeneic BMT in high risk non Hodgkin's lymphomas (NHL)
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Scientific Program and Abstracts T R E A T M E N T OF RELAPSED ALL WITH C O N V E N T I O N A L R E I N D U C T I O N T H E R A P Y , I N T E R M E D I A T E DOSE MTX ( I D M T X ) AND LATE I N T E N S I F I C A T I O N USING HIGH DOSE BUSULFAN, CYCLOPHOSPHAMIDE AND ALLOGENEIC BONE MARROW T R A N S P L A N T A T I O N ( B M T ) . C h . U r b a n , I . S l a v c , W.Kaulfersch, A.Hajek-Rosenmayr and I . T e u b l University School of Medicine Graz and Vienna, Austria Two p~tients with ALL, one with recurrent T - A L L and one with recurrent c - A L L ( m u l t i p l e CNS-relapses, 1st bone marrow and testicular relaps) were reinduced with the c u r r e n t ALL protocols (BFM protocol I and IV in pat.1 and Austrian Cooperative ALL protocol including frequent intrathecal drug administration and testicular irradiation in p a t . 2 , r e s p . ) . P r e v a lence to sanctuary sites was given d u r i n g maintenance therapy using Djerassi-MTX with BOMB in pat.1 and combined intrathecal and IDMTX plus 6-mercaptopurine in p a t . 2 ] . 15 and 10 months following the start of reinduction r e s p . , l a t e intensification using busulfan 4 mg/kg x 4 days and cyclophosphamide 50 mg/kg x 4 days was given, followed by allogeneic BMT as it is described for treatment of AML by G.W.Santos et a l . ( N . E n g I . J . M e d . 309: 1347,1983). The remission time in pat.1 is + 36 months and lasts already one year longer as the 1st remission achieved with conventional chemotherapy alone and is + 24 months in p a t . 2 . It is concluded~ that high dose busulfan is at least as effective in eradicating residual ALL as total body irradiation ( T B I ) , provided that sanctuary sites are being effectively treated before BMT. However the late side effects of high dose busulfan are expected to be less than those of T B I . A[LOGENEIC 8MT IN HIGH RISK NON HODGKIN'S LYMPHOMAS (NHL). Prepared by P.Ernst for the European Bone Marrow Transplantation Cooperative Group (EBMT). The FJnsen Institute, Copenhagen, Denmark. Although slgnificamt advances in the treatment of NHL have produced improvement in survival the prognosis For patients witb high risk disseminated disease is far from satisFactory. In leukemia improvement of s{mvival has been obtained after aggressive ehemoradiotherapy Followed by BMT.Few cases of BMT in NHL have been reported. We have analyzed the results of BMT For NHL performed by E8M]. Twenty-five grafts were recorded; 23 pts received a matched sibling marrow, while 2 received non identical marrow. Median age of pts: 19 years. 17 pts had !ymphoblastic lymphoma,] had BurkJtts lymphoma,3 NHL high grade, I had NHI intermediate grade. Stage at Dx:'IA('I),3A(1),4A(TO),4B(13). 13 pfis had BM involvement.All pts had received aggressive moderll therapy before 8M[.Time from D× to BMT was median 12 m. 24 pts were conditioned with chemotherapy and TBI before 8MT,I pt received chemotherapy alone. Disease status at BI4T and results of therapy. 9 pLs were grafted in I CR, all are surviving Jn CR 12-33 m. 9 pts were transplanted in 2-5 CR, 5 are alive in OR 13-19 m. 7 pts were transplanted in various stages of relapse, all have dimd after initially achie,,ing a CR.Major causes of death were: relapse (5),GVHD (2), IP (1),hemorrhage (I). ?attern of recovery of marrow function,acute and chF.GVHD and infectious prob]ems did not differ from what is seen in acute ]eukemia. ConchJsion: BMT is effective in high risk NHI with minimal residual disease. Results of treatment in advanced stages and with greater tumor burden are disappointing. REDUCTION AND REPOPULATION OF RECIPIENT T4+ AND Ta+ T LYMPHOCYTES IN ALLOGENEIC BONE MARROW TRANSPLANTATION. J.W. Gratama, R. Langlois van den Bergh, A. Naipal, F.E. Zwaan and G.C. de Gast. Departments of Immunohematology and Blood Bank, Pediatrics and Hematology, University Hospital, Leiden and Department of Hematology, University Hospitalv Utrecht, the Netherlands. In 8 recipients of allogeneic bone marrow grafts who had sex-mismatched donors, the reduction and subsequent repomulation of T4+ and T8+ T lymphocytes of recipient origin were studied. The origin of the donor/recipient T4+ and Ta+ T cells was studied using quinaerine staining of Y chromatin combined with T-cell typing for T4 and T8. Following chemoradiotherapy and bone marrow transplantation (BMT), T cells reached their nadir at a median of 5 (range i-8) days post BMT. Ta+ T cells decreased at a faster rate from the peripheral blood than T4+ T cells. The first T cells which appeared in the peripheral blood at day 12 were predominantly T4+, and a large part of them were of recipient origin. Thereafter, they gradually decreased, and the numbers of T cells of donor origin increased. In the patients who had no or only minor complications, T4+ and T8+ T cells of donor origin repopulated the blood at similar rates. This pattern, however, was modified by severe graft-versus-host disease or by cytomegalovirus infection. Our observation that radioresistant recipient T cells still are present in the circulation before the engraftment of donor bone marrow is relevant for T-cell depleted grafts which have a high risk of rejection hy sdch host-derived T cells.
Scientific Program and Abstracts T R E A T M E N T OF RELAPSED ALL WITH C O N V E N T I O N A L R E I N D U C T I O N T H E R A P Y , I N T E R M E D I A T E DOSE MTX ( I D M T X ) AND LATE I N T E N S I F I C A T I O N USING HIGH DOSE BUSULFAN, CYCLOPHOSPHAMIDE AND ALLOGENEIC BONE MARROW T R A N S P L A N T A T I O N ( B M T ) . C h . U r b a n , I . S l a v c , W.Kaulfersch, A.Hajek-Rosenmayr and I . T e u b l University School of Medicine Graz and Vienna, Austria Two p~tients with ALL, one with recurrent T - A L L and one with recurrent c - A L L ( m u l t i p l e CNS-relapses, 1st bone marrow and testicular relaps) were reinduced with the c u r r e n t ALL protocols (BFM protocol I and IV in pat.1 and Austrian Cooperative ALL protocol including frequent intrathecal drug administration and testicular irradiation in p a t . 2 , r e s p . ) . P r e v a lence to sanctuary sites was given d u r i n g maintenance therapy using Djerassi-MTX with BOMB in pat.1 and combined intrathecal and IDMTX plus 6-mercaptopurine in p a t . 2 ] . 15 and 10 months following the start of reinduction r e s p . , l a t e intensification using busulfan 4 mg/kg x 4 days and cyclophosphamide 50 mg/kg x 4 days was given, followed by allogeneic BMT as it is described for treatment of AML by G.W.Santos et a l . ( N . E n g I . J . M e d . 309: 1347,1983). The remission time in pat.1 is + 36 months and lasts already one year longer as the 1st remission achieved with conventional chemotherapy alone and is + 24 months in p a t . 2 . It is concluded~ that high dose busulfan is at least as effective in eradicating residual ALL as total body irradiation ( T B I ) , provided that sanctuary sites are being effectively treated before BMT. However the late side effects of high dose busulfan are expected to be less than those of T B I . A[LOGENEIC 8MT IN HIGH RISK NON HODGKIN'S LYMPHOMAS (NHL). Prepared by P.Ernst for the European Bone Marrow Transplantation Cooperative Group (EBMT). The FJnsen Institute, Copenhagen, Denmark. Although slgnificamt advances in the treatment of NHL have produced improvement in survival the prognosis For patients witb high risk disseminated disease is far from satisFactory. In leukemia improvement of s{mvival has been obtained after aggressive ehemoradiotherapy Followed by BMT.Few cases of BMT in NHL have been reported. We have analyzed the results of BMT For NHL performed by E8M]. Twenty-five grafts were recorded; 23 pts received a matched sibling marrow, while 2 received non identical marrow. Median age of pts: 19 years. 17 pts had !ymphoblastic lymphoma,] had BurkJtts lymphoma,3 NHL high grade, I had NHI intermediate grade. Stage at Dx:'IA('I),3A(1),4A(TO),4B(13). 13 pfis had BM involvement.All pts had received aggressive moderll therapy before 8M[.Time from D× to BMT was median 12 m. 24 pts were conditioned with chemotherapy and TBI before 8MT,I pt received chemotherapy alone. Disease status at BI4T and results of therapy. 9 pLs were grafted in I CR, all are surviving Jn CR 12-33 m. 9 pts were transplanted in 2-5 CR, 5 are alive in OR 13-19 m. 7 pts were transplanted in various stages of relapse, all have dimd after initially achie,,ing a CR.Major causes of death were: relapse (5),GVHD (2), IP (1),hemorrhage (I). ?attern of recovery of marrow function,acute and chF.GVHD and infectious prob]ems did not differ from what is seen in acute ]eukemia. ConchJsion: BMT is effective in high risk NHI with minimal residual disease. Results of treatment in advanced stages and with greater tumor burden are disappointing. REDUCTION AND REPOPULATION OF RECIPIENT T4+ AND Ta+ T LYMPHOCYTES IN ALLOGENEIC BONE MARROW TRANSPLANTATION. J.W. Gratama, R. Langlois van den Bergh, A. Naipal, F.E. Zwaan and G.C. de Gast. Departments of Immunohematology and Blood Bank, Pediatrics and Hematology, University Hospital, Leiden and Department of Hematology, University Hospitalv Utrecht, the Netherlands. In 8 recipients of allogeneic bone marrow grafts who had sex-mismatched donors, the reduction and subsequent repomulation of T4+ and T8+ T lymphocytes of recipient origin were studied. The origin of the donor/recipient T4+ and Ta+ T cells was studied using quinaerine staining of Y chromatin combined with T-cell typing for T4 and T8. Following chemoradiotherapy and bone marrow transplantation (BMT), T cells reached their nadir at a median of 5 (range i-8) days post BMT. Ta+ T cells decreased at a faster rate from the peripheral blood than T4+ T cells. The first T cells which appeared in the peripheral blood at day 12 were predominantly T4+, and a large part of them were of recipient origin. Thereafter, they gradually decreased, and the numbers of T cells of donor origin increased. In the patients who had no or only minor complications, T4+ and T8+ T cells of donor origin repopulated the blood at similar rates. This pattern, however, was modified by severe graft-versus-host disease or by cytomegalovirus infection. Our observation that radioresistant recipient T cells still are present in the circulation before the engraftment of donor bone marrow is relevant for T-cell depleted grafts which have a high risk of rejection hy sdch host-derived T cells.