Allogeneic hematopoietic stem cell (hsct) in patients with advanced hematological diseases using a non-myeloablative conditioning regimen

Choon Kee Lee, Raymond Hohl, Hayashi Masaki, Annette Schlueter, Elizabeth Field, Roger D. Gingrich

Research output: Contribution to journalArticle

Abstract

The use of nonmyeloablative regimens in patients (pts) not suitable for allogeneic HSCT because of poor performance status or advanced age has become an area of intense clinical research in the last few years. The optimum low intensity approach which maximizes engraftment and GVL while minimizing transplant related complications is yet to be defined. From April 1999 to May 2000 we treated 11 pts with fludarabine (25mg/m2x 3days) and cyclophosphamide (750mg/m2x3days) followed by HSCT from a G-CSF stimulated HLA identical sibling donor. As GVHD prophylaxis 8 pts received cyclosporin (CSA) and mini dose methotrexate, 2 pts CSA and mycophenolate mofetyl and 1 pt CSA and prednisone. CSA was given until T+60 then tappered off if no GVHD occured. Pts with persistent mixed donor/recipient chimerism or those with disease progression received escalation doses of DLL There were 4 females and 7 males with a median age of 57 years (range 39 to 67). Underlying diseases included: Secondary MDS (1), AML (3), Myeloma (1), CML (3), Amyloid (1 ), NHL (1) and CMMoL ( 1 ). Four pts had previous transplants ( 1 auto, 3 allo).Only one pt was in CR at time of therapy. A median of 5xl06/Kg CD34+ cells and 2xl08/Kg CD3+ cells were infused. Ten pts engrafted. Two pts died before day 28, one from disseminated aspergillus infection the other with presumed engraftment syndrome. Donor engraftment on day 30 was as follows (range[medianj): peripheral blood (80-95[87]%); bone marrow (80-95[90]%). The median time to ANC>0.5xlO'/L was 11 days (range 6 to 13) and to a platlet>20x 109/L was 14 days (range 6 to 18). Six pts experienced grade III-IV acute GVHD. DLI were given 10 two pts for disease progression. Four pts (36%) died before T+IOU . Two pts died after T+100, one with disease progression and another from GVHD. Five pts are alive at T+15, T+13, T+l 1, T+5 and T+3 months. Four (36%) pts are in CR ( one after receiving DLI for cytogenetic relapse). Conclusion: These data confirm that engraftment of allogeneic peripheral blood can be achieved with a low intensity regimen and that remissions occur in some pts with advanced hematological malignancies. GVHD remains a serious complication of this approach.

Original languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART II
StatePublished - Dec 1 2000

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Hematologic Diseases
Hematopoietic Stem Cells
Stem cells
Transplants
Blood
Emitter coupled logic circuits
Aspergillus
Granulocyte Colony-Stimulating Factor
Prednisone
Amyloid
Methotrexate
Cyclophosphamide
Cyclosporine
Bone
Disease Progression
Tissue Donors
Conditioning (Psychology)
Chimerism
Hematologic Neoplasms
Cytogenetics

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Lee, Choon Kee ; Hohl, Raymond ; Masaki, Hayashi ; Schlueter, Annette ; Field, Elizabeth ; Gingrich, Roger D. / Allogeneic hematopoietic stem cell (hsct) in patients with advanced hematological diseases using a non-myeloablative conditioning regimen. In: Blood. 2000 ; Vol. 96, No. 11 PART II.
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abstract = "The use of nonmyeloablative regimens in patients (pts) not suitable for allogeneic HSCT because of poor performance status or advanced age has become an area of intense clinical research in the last few years. The optimum low intensity approach which maximizes engraftment and GVL while minimizing transplant related complications is yet to be defined. From April 1999 to May 2000 we treated 11 pts with fludarabine (25mg/m2x 3days) and cyclophosphamide (750mg/m2x3days) followed by HSCT from a G-CSF stimulated HLA identical sibling donor. As GVHD prophylaxis 8 pts received cyclosporin (CSA) and mini dose methotrexate, 2 pts CSA and mycophenolate mofetyl and 1 pt CSA and prednisone. CSA was given until T+60 then tappered off if no GVHD occured. Pts with persistent mixed donor/recipient chimerism or those with disease progression received escalation doses of DLL There were 4 females and 7 males with a median age of 57 years (range 39 to 67). Underlying diseases included: Secondary MDS (1), AML (3), Myeloma (1), CML (3), Amyloid (1 ), NHL (1) and CMMoL ( 1 ). Four pts had previous transplants ( 1 auto, 3 allo).Only one pt was in CR at time of therapy. A median of 5xl06/Kg CD34+ cells and 2xl08/Kg CD3+ cells were infused. Ten pts engrafted. Two pts died before day 28, one from disseminated aspergillus infection the other with presumed engraftment syndrome. Donor engraftment on day 30 was as follows (range[medianj): peripheral blood (80-95[87]{\%}); bone marrow (80-95[90]{\%}). The median time to ANC>0.5xlO'/L was 11 days (range 6 to 13) and to a platlet>20x 109/L was 14 days (range 6 to 18). Six pts experienced grade III-IV acute GVHD. DLI were given 10 two pts for disease progression. Four pts (36{\%}) died before T+IOU . Two pts died after T+100, one with disease progression and another from GVHD. Five pts are alive at T+15, T+13, T+l 1, T+5 and T+3 months. Four (36{\%}) pts are in CR ( one after receiving DLI for cytogenetic relapse). Conclusion: These data confirm that engraftment of allogeneic peripheral blood can be achieved with a low intensity regimen and that remissions occur in some pts with advanced hematological malignancies. GVHD remains a serious complication of this approach.",
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Allogeneic hematopoietic stem cell (hsct) in patients with advanced hematological diseases using a non-myeloablative conditioning regimen. / Lee, Choon Kee; Hohl, Raymond; Masaki, Hayashi; Schlueter, Annette; Field, Elizabeth; Gingrich, Roger D.

In: Blood, Vol. 96, No. 11 PART II, 01.12.2000.

Research output: Contribution to journalArticle

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AU - Hohl, Raymond

AU - Masaki, Hayashi

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AU - Field, Elizabeth

AU - Gingrich, Roger D.

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N2 - The use of nonmyeloablative regimens in patients (pts) not suitable for allogeneic HSCT because of poor performance status or advanced age has become an area of intense clinical research in the last few years. The optimum low intensity approach which maximizes engraftment and GVL while minimizing transplant related complications is yet to be defined. From April 1999 to May 2000 we treated 11 pts with fludarabine (25mg/m2x 3days) and cyclophosphamide (750mg/m2x3days) followed by HSCT from a G-CSF stimulated HLA identical sibling donor. As GVHD prophylaxis 8 pts received cyclosporin (CSA) and mini dose methotrexate, 2 pts CSA and mycophenolate mofetyl and 1 pt CSA and prednisone. CSA was given until T+60 then tappered off if no GVHD occured. Pts with persistent mixed donor/recipient chimerism or those with disease progression received escalation doses of DLL There were 4 females and 7 males with a median age of 57 years (range 39 to 67). Underlying diseases included: Secondary MDS (1), AML (3), Myeloma (1), CML (3), Amyloid (1 ), NHL (1) and CMMoL ( 1 ). Four pts had previous transplants ( 1 auto, 3 allo).Only one pt was in CR at time of therapy. A median of 5xl06/Kg CD34+ cells and 2xl08/Kg CD3+ cells were infused. Ten pts engrafted. Two pts died before day 28, one from disseminated aspergillus infection the other with presumed engraftment syndrome. Donor engraftment on day 30 was as follows (range[medianj): peripheral blood (80-95[87]%); bone marrow (80-95[90]%). The median time to ANC>0.5xlO'/L was 11 days (range 6 to 13) and to a platlet>20x 109/L was 14 days (range 6 to 18). Six pts experienced grade III-IV acute GVHD. DLI were given 10 two pts for disease progression. Four pts (36%) died before T+IOU . Two pts died after T+100, one with disease progression and another from GVHD. Five pts are alive at T+15, T+13, T+l 1, T+5 and T+3 months. Four (36%) pts are in CR ( one after receiving DLI for cytogenetic relapse). Conclusion: These data confirm that engraftment of allogeneic peripheral blood can be achieved with a low intensity regimen and that remissions occur in some pts with advanced hematological malignancies. GVHD remains a serious complication of this approach.

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