INTRA-BONE DONOR LYMPHOCYTE INFUSION IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES RELAPSING POST ALLOHSCT
(Abstract release date: 05/19/16)
EHA Library. Lange A. 06/09/16; 132666; E1117
Prof. Dr. Andrzej Lange
Contributions
Contributions
Abstract
Abstract: E1117
Type: Eposter Presentation
Background
Donor Lymphocyte Infusion (DLI) is effective in a proportion of patients with leukaemia relapsing post alloHSCT. This effect is over-paid by a high risk of severe aGvHD. Ikehara and Frassoni showed the efficacy of the intra-bone (IB) marrow hematopoietic stem cell transplantation associates with a prompt hematopoietic reconstitution and a low risk of aGvHD in animal experiments and in human setting, respectively. Recurrence and GvHD are major causes of treatment failure post alloHSCT.
Aims
In this study we evaluated a novel technique for relapse treatment in which donor lymphocytes are directly injected into the patient’s bone marrow cavity. This study was approved by the local ethic committee.
Methods
Four patients: 3 with AML (2 alloSIB: 50 years old, female, normal karyotype; 22 years, male 7q31 del., CNS lesions post trauma; and one alloMUD: 25 years, male FLT3 ITD), and one with CLL, 64 years old male, TP53 del, chronic EBV infection. FLT3 ITD AML case relapsed 9 months, other AML cases 2 and 3 yrs and CLL patient 7 years post alloHSCT. The salvage chemotherapy included FLAG for FLT3 ITD case, anti-CD20 MoAb for CLL case, two other AML cases received DLI upfront. All received IB DLI (according to the escalating dose regimen starting from 10E6 for the first and 10E7 for the second and usually 5 times 10E7 CD3+ lymphocytes for the third dose [cells/kg body weight]). The intervals between IB DLI in 3 patients varied from 1 to 2 months being longer in one AML case in which between IB DLI 5’ azacitidine was administrated. The cells for DLI were obtained from the primary PBPC transplant material in alloMUD AML case and from unstimulated PBPC in alloSIB and in two AML cases as well as in one CLL case. The cells were injected directly to the bone marrow cavity under local anaesthesia and a low molecular Heparin prophylaxis.
Results
1) At 30 check points post IB DLI the marrow and blood lymphocyte profile was investigated in 4 patients. We found the prevalence of CD8+ cells proportions in the marrow over those in the blood (median: 24.3% vs 23.8%, p<0.004) but in particular the prevalence of CD279+ lymphocytes (16.3% vs 9.5%, p<0.001) and those CD8+CD279+ (6.5% vs 3.2%, p<0.001).2) In CLL cases there was a drop in the count of blood lymphocytes, cellularity of the marrow also decreased and the patient was haematologically stable. The examination 8 months after the last DLI revealed 3300/µl CD5+CD19+ lymphocytes in the blood. The level which was also seen soon after the completion of the IB DLI treatment.3) AML FLT3 ITD patients responding well to the FLAG salvage therapy followed by IB DLI is leukaemia free 3 months after the relapse, two other cases were stable haematologically (ECOG1) but an increase in the proportions of myeloblasts from 23% to 34% seen during 7 and 6 months of observation time which included IB DLI treatment prompted us to perform the second transplantation in one case (uncomplicated) and to schedule the second transplant in the other case.
Conclusion
1) The observation of four patients they completed IB DLI suggests that it is safe procedure and GvHD was not observed.2) The anti-leukemic effect was seen in CLL case and a stabilization of the haematopoiesis was seen in two patients receiving IB DLI being not in remission. AML FLT3 ITD positive case relapsing soon after transplant responded to the FLAG regimen followed by IB DLI.3) The higher proportions of CD8+CD279+ lymphocytes in the marrow as compared to the blood suggest the presence in the marrow the cells actively involved in the surveillance of leukaemia.Supported by INNOMED/I/1/NCBR/2014 grant.
Session topic: E-poster
Keyword(s): Donor lymphocyte infusion, Relapse
Type: Eposter Presentation
Background
Donor Lymphocyte Infusion (DLI) is effective in a proportion of patients with leukaemia relapsing post alloHSCT. This effect is over-paid by a high risk of severe aGvHD. Ikehara and Frassoni showed the efficacy of the intra-bone (IB) marrow hematopoietic stem cell transplantation associates with a prompt hematopoietic reconstitution and a low risk of aGvHD in animal experiments and in human setting, respectively. Recurrence and GvHD are major causes of treatment failure post alloHSCT.
Aims
In this study we evaluated a novel technique for relapse treatment in which donor lymphocytes are directly injected into the patient’s bone marrow cavity. This study was approved by the local ethic committee.
Methods
Four patients: 3 with AML (2 alloSIB: 50 years old, female, normal karyotype; 22 years, male 7q31 del., CNS lesions post trauma; and one alloMUD: 25 years, male FLT3 ITD), and one with CLL, 64 years old male, TP53 del, chronic EBV infection. FLT3 ITD AML case relapsed 9 months, other AML cases 2 and 3 yrs and CLL patient 7 years post alloHSCT. The salvage chemotherapy included FLAG for FLT3 ITD case, anti-CD20 MoAb for CLL case, two other AML cases received DLI upfront. All received IB DLI (according to the escalating dose regimen starting from 10E6 for the first and 10E7 for the second and usually 5 times 10E7 CD3+ lymphocytes for the third dose [cells/kg body weight]). The intervals between IB DLI in 3 patients varied from 1 to 2 months being longer in one AML case in which between IB DLI 5’ azacitidine was administrated. The cells for DLI were obtained from the primary PBPC transplant material in alloMUD AML case and from unstimulated PBPC in alloSIB and in two AML cases as well as in one CLL case. The cells were injected directly to the bone marrow cavity under local anaesthesia and a low molecular Heparin prophylaxis.
Results
1) At 30 check points post IB DLI the marrow and blood lymphocyte profile was investigated in 4 patients. We found the prevalence of CD8+ cells proportions in the marrow over those in the blood (median: 24.3% vs 23.8%, p<0.004) but in particular the prevalence of CD279+ lymphocytes (16.3% vs 9.5%, p<0.001) and those CD8+CD279+ (6.5% vs 3.2%, p<0.001).2) In CLL cases there was a drop in the count of blood lymphocytes, cellularity of the marrow also decreased and the patient was haematologically stable. The examination 8 months after the last DLI revealed 3300/µl CD5+CD19+ lymphocytes in the blood. The level which was also seen soon after the completion of the IB DLI treatment.3) AML FLT3 ITD patients responding well to the FLAG salvage therapy followed by IB DLI is leukaemia free 3 months after the relapse, two other cases were stable haematologically (ECOG1) but an increase in the proportions of myeloblasts from 23% to 34% seen during 7 and 6 months of observation time which included IB DLI treatment prompted us to perform the second transplantation in one case (uncomplicated) and to schedule the second transplant in the other case.
Conclusion
1) The observation of four patients they completed IB DLI suggests that it is safe procedure and GvHD was not observed.2) The anti-leukemic effect was seen in CLL case and a stabilization of the haematopoiesis was seen in two patients receiving IB DLI being not in remission. AML FLT3 ITD positive case relapsing soon after transplant responded to the FLAG regimen followed by IB DLI.3) The higher proportions of CD8+CD279+ lymphocytes in the marrow as compared to the blood suggest the presence in the marrow the cells actively involved in the surveillance of leukaemia.Supported by INNOMED/I/1/NCBR/2014 grant.
Session topic: E-poster
Keyword(s): Donor lymphocyte infusion, Relapse
Abstract: E1117
Type: Eposter Presentation
Background
Donor Lymphocyte Infusion (DLI) is effective in a proportion of patients with leukaemia relapsing post alloHSCT. This effect is over-paid by a high risk of severe aGvHD. Ikehara and Frassoni showed the efficacy of the intra-bone (IB) marrow hematopoietic stem cell transplantation associates with a prompt hematopoietic reconstitution and a low risk of aGvHD in animal experiments and in human setting, respectively. Recurrence and GvHD are major causes of treatment failure post alloHSCT.
Aims
In this study we evaluated a novel technique for relapse treatment in which donor lymphocytes are directly injected into the patient’s bone marrow cavity. This study was approved by the local ethic committee.
Methods
Four patients: 3 with AML (2 alloSIB: 50 years old, female, normal karyotype; 22 years, male 7q31 del., CNS lesions post trauma; and one alloMUD: 25 years, male FLT3 ITD), and one with CLL, 64 years old male, TP53 del, chronic EBV infection. FLT3 ITD AML case relapsed 9 months, other AML cases 2 and 3 yrs and CLL patient 7 years post alloHSCT. The salvage chemotherapy included FLAG for FLT3 ITD case, anti-CD20 MoAb for CLL case, two other AML cases received DLI upfront. All received IB DLI (according to the escalating dose regimen starting from 10E6 for the first and 10E7 for the second and usually 5 times 10E7 CD3+ lymphocytes for the third dose [cells/kg body weight]). The intervals between IB DLI in 3 patients varied from 1 to 2 months being longer in one AML case in which between IB DLI 5’ azacitidine was administrated. The cells for DLI were obtained from the primary PBPC transplant material in alloMUD AML case and from unstimulated PBPC in alloSIB and in two AML cases as well as in one CLL case. The cells were injected directly to the bone marrow cavity under local anaesthesia and a low molecular Heparin prophylaxis.
Results
1) At 30 check points post IB DLI the marrow and blood lymphocyte profile was investigated in 4 patients. We found the prevalence of CD8+ cells proportions in the marrow over those in the blood (median: 24.3% vs 23.8%, p<0.004) but in particular the prevalence of CD279+ lymphocytes (16.3% vs 9.5%, p<0.001) and those CD8+CD279+ (6.5% vs 3.2%, p<0.001).2) In CLL cases there was a drop in the count of blood lymphocytes, cellularity of the marrow also decreased and the patient was haematologically stable. The examination 8 months after the last DLI revealed 3300/µl CD5+CD19+ lymphocytes in the blood. The level which was also seen soon after the completion of the IB DLI treatment.3) AML FLT3 ITD patients responding well to the FLAG salvage therapy followed by IB DLI is leukaemia free 3 months after the relapse, two other cases were stable haematologically (ECOG1) but an increase in the proportions of myeloblasts from 23% to 34% seen during 7 and 6 months of observation time which included IB DLI treatment prompted us to perform the second transplantation in one case (uncomplicated) and to schedule the second transplant in the other case.
Conclusion
1) The observation of four patients they completed IB DLI suggests that it is safe procedure and GvHD was not observed.2) The anti-leukemic effect was seen in CLL case and a stabilization of the haematopoiesis was seen in two patients receiving IB DLI being not in remission. AML FLT3 ITD positive case relapsing soon after transplant responded to the FLAG regimen followed by IB DLI.3) The higher proportions of CD8+CD279+ lymphocytes in the marrow as compared to the blood suggest the presence in the marrow the cells actively involved in the surveillance of leukaemia.Supported by INNOMED/I/1/NCBR/2014 grant.
Session topic: E-poster
Keyword(s): Donor lymphocyte infusion, Relapse
Type: Eposter Presentation
Background
Donor Lymphocyte Infusion (DLI) is effective in a proportion of patients with leukaemia relapsing post alloHSCT. This effect is over-paid by a high risk of severe aGvHD. Ikehara and Frassoni showed the efficacy of the intra-bone (IB) marrow hematopoietic stem cell transplantation associates with a prompt hematopoietic reconstitution and a low risk of aGvHD in animal experiments and in human setting, respectively. Recurrence and GvHD are major causes of treatment failure post alloHSCT.
Aims
In this study we evaluated a novel technique for relapse treatment in which donor lymphocytes are directly injected into the patient’s bone marrow cavity. This study was approved by the local ethic committee.
Methods
Four patients: 3 with AML (2 alloSIB: 50 years old, female, normal karyotype; 22 years, male 7q31 del., CNS lesions post trauma; and one alloMUD: 25 years, male FLT3 ITD), and one with CLL, 64 years old male, TP53 del, chronic EBV infection. FLT3 ITD AML case relapsed 9 months, other AML cases 2 and 3 yrs and CLL patient 7 years post alloHSCT. The salvage chemotherapy included FLAG for FLT3 ITD case, anti-CD20 MoAb for CLL case, two other AML cases received DLI upfront. All received IB DLI (according to the escalating dose regimen starting from 10E6 for the first and 10E7 for the second and usually 5 times 10E7 CD3+ lymphocytes for the third dose [cells/kg body weight]). The intervals between IB DLI in 3 patients varied from 1 to 2 months being longer in one AML case in which between IB DLI 5’ azacitidine was administrated. The cells for DLI were obtained from the primary PBPC transplant material in alloMUD AML case and from unstimulated PBPC in alloSIB and in two AML cases as well as in one CLL case. The cells were injected directly to the bone marrow cavity under local anaesthesia and a low molecular Heparin prophylaxis.
Results
1) At 30 check points post IB DLI the marrow and blood lymphocyte profile was investigated in 4 patients. We found the prevalence of CD8+ cells proportions in the marrow over those in the blood (median: 24.3% vs 23.8%, p<0.004) but in particular the prevalence of CD279+ lymphocytes (16.3% vs 9.5%, p<0.001) and those CD8+CD279+ (6.5% vs 3.2%, p<0.001).2) In CLL cases there was a drop in the count of blood lymphocytes, cellularity of the marrow also decreased and the patient was haematologically stable. The examination 8 months after the last DLI revealed 3300/µl CD5+CD19+ lymphocytes in the blood. The level which was also seen soon after the completion of the IB DLI treatment.3) AML FLT3 ITD patients responding well to the FLAG salvage therapy followed by IB DLI is leukaemia free 3 months after the relapse, two other cases were stable haematologically (ECOG1) but an increase in the proportions of myeloblasts from 23% to 34% seen during 7 and 6 months of observation time which included IB DLI treatment prompted us to perform the second transplantation in one case (uncomplicated) and to schedule the second transplant in the other case.
Conclusion
1) The observation of four patients they completed IB DLI suggests that it is safe procedure and GvHD was not observed.2) The anti-leukemic effect was seen in CLL case and a stabilization of the haematopoiesis was seen in two patients receiving IB DLI being not in remission. AML FLT3 ITD positive case relapsing soon after transplant responded to the FLAG regimen followed by IB DLI.3) The higher proportions of CD8+CD279+ lymphocytes in the marrow as compared to the blood suggest the presence in the marrow the cells actively involved in the surveillance of leukaemia.Supported by INNOMED/I/1/NCBR/2014 grant.
Session topic: E-poster
Keyword(s): Donor lymphocyte infusion, Relapse
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