Influence of mixed chimerism on the results of allogeneic bone marrow transplantation for leukemia

Abstract Serial cytogenetic studies were performed on 60 leukemic recipients of HLA-matched bone marrow transplants (BMT) who were prepared by high doses of alkylating agents and fractionated total body irradiation (TBI). Forty-three patients were recipients of untreated BMT and 17 were recipients of T-depleted BMT. Donor or host mitoses were identified by examination of sex chromosomes in 54 patients or by evaluation of the polymorphism of other chromosomes after specific banding in six patients. Mixed lymphoid chimerism (MLC) was identified in 29 patients and full donor lymphoid chimerism (FDLC) in 29 patients. Complete donor hematopoiesis was recovered in most patients after 12 months, but two T-depleted patients had persistent host cells at 46 and 52 months after the graft. Acute graft-versus-host disease was significantly less frequent in patients with MLC, especially when more than 10% of residual lymphoid cells were detected. The probability of relapse and survival was identical in patients with MLC and FDLC, except in patients with chronic myeloid leukemia where MLC was significantly associated with an increased risk of relapse.

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Influence of mixed chimerism on the results of allogeneic bone marrow transplantation for leukemia

Blood ◽

10.1182/blood.v78.11.3103.bloodjournal78113103 ◽

1991 ◽

Vol 78 (11) ◽

pp. 3103-3106 ◽

Cited By ~ 1

Author(s):

MF Bertheas ◽

M Lafage ◽

P Levy ◽

D Blaise ◽

AM Stoppa ◽

...

Keyword(s):

Bone Marrow ◽

Alkylating Agents ◽

Allogeneic Bone Marrow Transplantation ◽

Lymphoid Cells ◽

Host Cells ◽

Mixed Chimerism ◽

Allogeneic Bone ◽

Increased Risk ◽

High Doses ◽

Total Body

Serial cytogenetic studies were performed on 60 leukemic recipients of HLA-matched bone marrow transplants (BMT) who were prepared by high doses of alkylating agents and fractionated total body irradiation (TBI). Forty-three patients were recipients of untreated BMT and 17 were recipients of T-depleted BMT. Donor or host mitoses were identified by examination of sex chromosomes in 54 patients or by evaluation of the polymorphism of other chromosomes after specific banding in six patients. Mixed lymphoid chimerism (MLC) was identified in 29 patients and full donor lymphoid chimerism (FDLC) in 29 patients. Complete donor hematopoiesis was recovered in most patients after 12 months, but two T-depleted patients had persistent host cells at 46 and 52 months after the graft. Acute graft-versus-host disease was significantly less frequent in patients with MLC, especially when more than 10% of residual lymphoid cells were detected. The probability of relapse and survival was identical in patients with MLC and FDLC, except in patients with chronic myeloid leukemia where MLC was significantly associated with an increased risk of relapse.

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Partial chimerism after T-cell-depleted allogeneic bone marrow transplantation in leukemic HLA-matched patients: a cytogenetic documentation

Blood ◽

10.1182/blood.v72.1.89.bloodjournal72189 ◽

1988 ◽

Vol 72 (1) ◽

pp. 89-93

Author(s):

MF Bertheas ◽

D Maraninchi ◽

M Lafage ◽

J Fraisse ◽

D Blaise ◽

...

Keyword(s):

Bone Marrow ◽

T Cell ◽

High Frequency ◽

Alkylating Agents ◽

Allogeneic Bone Marrow Transplantation ◽

Control Group ◽

Allogeneic Bone ◽

High Doses ◽

Total Body ◽

Mixed Chimeras

We evaluated serially by cytogenetics the blood and marrow chimerism of 38 leukemic recipients of HLA-matched bone marrow transplants (BMT) who were prepared by high doses of alkylating agents and fractionated total- body irradiation (2.2 Gy X 5). Donor or host mitoses were identified by examination of sex chromosomes in 32 patients or by evaluation of the polymorphism of other chromosomes after specific banding in six patients. Twenty-four patients were recipients of untreated BMT, and 14 were recipients of T-cell-depleted BMT. In the 24 patients who received untreated BMT, all showed successful engraftment, and only three had a transient mixed chimera. In the 14 recipients of T-cell-depleted BMTs, four rejected their grafts, and seven had mixed chimeras; these mixed chimeras were more frequent in blood lymphocytes than in marrow cells and could be detected up to 26 months after BMT. This high frequency of partial chimerism after T-cell-depleted BMT by comparison with a control group suggests that the donor's T cells play an important role in the eradication of host residual hematopoiesis after allogeneic BMT.

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Partial chimerism after T-cell-depleted allogeneic bone marrow transplantation in leukemic HLA-matched patients: a cytogenetic documentation

Blood ◽

10.1182/blood.v72.1.89.89 ◽

1988 ◽

Vol 72 (1) ◽

pp. 89-93 ◽

Cited By ~ 27

Author(s):

MF Bertheas ◽

D Maraninchi ◽

M Lafage ◽

J Fraisse ◽

D Blaise ◽

...

Keyword(s):

Bone Marrow ◽

T Cell ◽

High Frequency ◽

Alkylating Agents ◽

Allogeneic Bone Marrow Transplantation ◽

Control Group ◽

Allogeneic Bone ◽

High Doses ◽

Total Body ◽

Mixed Chimeras

Abstract We evaluated serially by cytogenetics the blood and marrow chimerism of 38 leukemic recipients of HLA-matched bone marrow transplants (BMT) who were prepared by high doses of alkylating agents and fractionated total- body irradiation (2.2 Gy X 5). Donor or host mitoses were identified by examination of sex chromosomes in 32 patients or by evaluation of the polymorphism of other chromosomes after specific banding in six patients. Twenty-four patients were recipients of untreated BMT, and 14 were recipients of T-cell-depleted BMT. In the 24 patients who received untreated BMT, all showed successful engraftment, and only three had a transient mixed chimera. In the 14 recipients of T-cell-depleted BMTs, four rejected their grafts, and seven had mixed chimeras; these mixed chimeras were more frequent in blood lymphocytes than in marrow cells and could be detected up to 26 months after BMT. This high frequency of partial chimerism after T-cell-depleted BMT by comparison with a control group suggests that the donor's T cells play an important role in the eradication of host residual hematopoiesis after allogeneic BMT.

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Evolution of mixed chimerism after allogeneic bone marrow transplantation as determined on granulocytes and mononuclear cells by the polymerase chain reaction

Blood ◽

10.1182/blood.v79.10.2775.2775 ◽

1992 ◽

Vol 79 (10) ◽

pp. 2775-2783 ◽

Cited By ~ 3

Author(s):

E Roux ◽

C Helg ◽

B Chapuis ◽

M Jeannet ◽

E Roosnek

Keyword(s):

Bone Marrow ◽

Polymerase Chain Reaction ◽

Bone Marrow Transplantation ◽

Mononuclear Cells ◽

Allogeneic Bone Marrow Transplantation ◽

Host Cells ◽

Mixed Chimerism ◽

Allogeneic Bone ◽

Chain Reaction ◽

Polymerase Chain

Abstract To evaluate the clinical relevance of mixed chimerism (MC) after allogeneic bone marrow transplantation (BMT), we developed a method based on amplification of DNA minisatellites by the polymerase chain reaction (PCR). This sensitive method by which MC lower than 1% can be detected is applicable to any patient-donor pair. Furthermore, because the analysis requires only small amounts of DNA, it allowed us to analyze samples early after BMT and during graft rejection. Results were obtained within 48 hours after blood sampling. Determination of MC in granulocytes (GR) and in mononuclear cells (Mnc) was performed in 20 patients treated for various hematologic malignancies. In patients who received untreated BM, recipient cells disappeared rapidly after BMT. In patients transplanted with T-cell-depleted BM, MC occurred in 15 of 16 cases. The percentage of host Mnc was always significantly higher than the percentage of host GR. The evolution of MC in patients who received T-cell-depleted marrow showed distinct patterns depending on whether patients remained in continuous complete remission, relapsed, or rejected their grafts. During complete remission, a relatively stable and significant number of host cells could be detected during the first 2 years after transplantation. Thereafter, their number decreased, but even after 4 years, low numbers of host cells could persist. When the patients relapsed, an increase in host Mnc was monitored without significant changes in the number of donor Mnc. In contrast, after the relapse, donor GR were no longer detected. Two cases of graft rejection were studied. Directly after the onset of the rejection, donor GR and Mnc disappeared rapidly. During that period, no significant changes in the number of host Mnc were detected.

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Fractionated total body irradiation and high-dose VP 16-213 followed by allogeneic bone marrow transplantation in advanced leukemias

Blood ◽

10.1182/blood.v72.5.1567.bloodjournal7251567 ◽

1988 ◽

Vol 72 (5) ◽

pp. 1567-1573 ◽

Cited By ~ 1

Author(s):

N Schmitz ◽

W Gassmann ◽

M Rister ◽

W Johannson ◽

M Suttorp ◽

...

Keyword(s):

Bone Marrow ◽

Total Body Irradiation ◽

Allogeneic Bone Marrow Transplantation ◽

Allogeneic Bone Marrow ◽

Myelogenous Leukemia ◽

Refractory Anemia ◽

High Dose ◽

Allogeneic Bone ◽

Increased Risk ◽

Total Body

Thirty-eight patients (median age, 21 years) with acute nonlymphoblastic leukemia (ANLL) (17 patients), acute lymphoblastic leukemia/lymphoma (ALL) (18 patients), chronic myelogenous leukemia (two patients), and refractory anemia received allogeneic bone marrow transplants from HLA-identical sibling donors or a one-antigen- mismatched brother (one patient) after a preparatory regimen consisting of fractionated total body irradiation and high-dose VP 16–213 (60 to 70 mg/kg body weight). Of the 33 patients with acute leukemia who received grafts from HLA-identical donors, three patients with ANLL received transplants in first remission and one patient with standard- risk ALL received a graft while in second remission. All other patients were in more advanced stages of their disease or exhibited other high- risk features. At the time of analysis, 20 of the 33 patients were alive, with 19 of them remaining in continued complete remission for 6 to 35 months (median, 18 months). The 3-year actuarial disease-free survival rate of 56.6% +/- 9.7% (SE) and the actuarial relapse rate of 11.9% +/- 6.8% (SE) demonstrate that the combination of fractionated total body irradiation and high-dose VP 16 is an effective mode of therapy in patients with advanced leukemias. Preliminary experience cautions against the use of VP 16 instead of cyclophosphamide in any clinical situation carrying an increased risk of graft rejection because the immunosuppressive potency of VP 16 is largely untested but may be inferior to that of cyclophosphamide.

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Fractionated total body irradiation and high-dose VP 16-213 followed by allogeneic bone marrow transplantation in advanced leukemias

Blood ◽

10.1182/blood.v72.5.1567.1567 ◽

1988 ◽

Vol 72 (5) ◽

pp. 1567-1573 ◽

Cited By ~ 55

Author(s):

N Schmitz ◽

W Gassmann ◽

M Rister ◽

W Johannson ◽

M Suttorp ◽

...

Keyword(s):

Bone Marrow ◽

Total Body Irradiation ◽

Allogeneic Bone Marrow Transplantation ◽

Allogeneic Bone Marrow ◽

Myelogenous Leukemia ◽

Refractory Anemia ◽

High Dose ◽

Allogeneic Bone ◽

Increased Risk ◽

Total Body

Abstract Thirty-eight patients (median age, 21 years) with acute nonlymphoblastic leukemia (ANLL) (17 patients), acute lymphoblastic leukemia/lymphoma (ALL) (18 patients), chronic myelogenous leukemia (two patients), and refractory anemia received allogeneic bone marrow transplants from HLA-identical sibling donors or a one-antigen- mismatched brother (one patient) after a preparatory regimen consisting of fractionated total body irradiation and high-dose VP 16–213 (60 to 70 mg/kg body weight). Of the 33 patients with acute leukemia who received grafts from HLA-identical donors, three patients with ANLL received transplants in first remission and one patient with standard- risk ALL received a graft while in second remission. All other patients were in more advanced stages of their disease or exhibited other high- risk features. At the time of analysis, 20 of the 33 patients were alive, with 19 of them remaining in continued complete remission for 6 to 35 months (median, 18 months). The 3-year actuarial disease-free survival rate of 56.6% +/- 9.7% (SE) and the actuarial relapse rate of 11.9% +/- 6.8% (SE) demonstrate that the combination of fractionated total body irradiation and high-dose VP 16 is an effective mode of therapy in patients with advanced leukemias. Preliminary experience cautions against the use of VP 16 instead of cyclophosphamide in any clinical situation carrying an increased risk of graft rejection because the immunosuppressive potency of VP 16 is largely untested but may be inferior to that of cyclophosphamide.

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Evolution of mixed chimerism after allogeneic bone marrow transplantation as determined on granulocytes and mononuclear cells by the polymerase chain reaction

Blood ◽

10.1182/blood.v79.10.2775.bloodjournal79102775 ◽

1992 ◽

Vol 79 (10) ◽

pp. 2775-2783 ◽

Cited By ~ 41

Author(s):

E Roux ◽

C Helg ◽

B Chapuis ◽

M Jeannet ◽

E Roosnek

Keyword(s):

Bone Marrow ◽

Polymerase Chain Reaction ◽

Bone Marrow Transplantation ◽

Mononuclear Cells ◽

Allogeneic Bone Marrow Transplantation ◽

Host Cells ◽

Mixed Chimerism ◽

Allogeneic Bone ◽

Chain Reaction ◽

Polymerase Chain

To evaluate the clinical relevance of mixed chimerism (MC) after allogeneic bone marrow transplantation (BMT), we developed a method based on amplification of DNA minisatellites by the polymerase chain reaction (PCR). This sensitive method by which MC lower than 1% can be detected is applicable to any patient-donor pair. Furthermore, because the analysis requires only small amounts of DNA, it allowed us to analyze samples early after BMT and during graft rejection. Results were obtained within 48 hours after blood sampling. Determination of MC in granulocytes (GR) and in mononuclear cells (Mnc) was performed in 20 patients treated for various hematologic malignancies. In patients who received untreated BM, recipient cells disappeared rapidly after BMT. In patients transplanted with T-cell-depleted BM, MC occurred in 15 of 16 cases. The percentage of host Mnc was always significantly higher than the percentage of host GR. The evolution of MC in patients who received T-cell-depleted marrow showed distinct patterns depending on whether patients remained in continuous complete remission, relapsed, or rejected their grafts. During complete remission, a relatively stable and significant number of host cells could be detected during the first 2 years after transplantation. Thereafter, their number decreased, but even after 4 years, low numbers of host cells could persist. When the patients relapsed, an increase in host Mnc was monitored without significant changes in the number of donor Mnc. In contrast, after the relapse, donor GR were no longer detected. Two cases of graft rejection were studied. Directly after the onset of the rejection, donor GR and Mnc disappeared rapidly. During that period, no significant changes in the number of host Mnc were detected.

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