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

Mf, Bertheas; Maraninchi, D; Lafage, Marina; Fraisse, J; Blaise, Didier; Stoppa, A. M.; Gautier, Michel; Cp, Brizard; Gaspard, MH; Novakovitch, G

doi:10.1182/blood.v72.1.89.89

Cited by 46 publications

(8 citation statements)

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“…Using red blood cell phenotyping and cytogenetic analysis of the bone marrow, evaluation of chimaerism at 6 months and 1 year after BMT showed high incidences of mixed chimaerism. These findings are comparable with other chimaerism studies after transplantation with T-cell-depleted marrow grafts (Bertheas et al, 1988;Roy et al, 1990;Schattenberg et al, 1989). In a previous analysis we showed that mixed chimaerism at 6 months after BMT was not correlated with higher incidence of relapse (Schattenberg et al, 1990.…”

Section: Discussionsupporting

confidence: 91%

Outcome of transplantation for standard‐risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen

Schaap¹,

Schattenberg²,

Bär³

et al. 1997

Br J Haematol

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Summary.One hundred and eighty-one consecutive patients with standard-risk leukaemia were transplanted with HLAidentical sibling grafts depleted of lymphocytes using counterflow centrifugation. In 116 patients, standard conditioning was intensified by the addition of anthracyclines.Multivariate analysis revealed significantly more acute GVHD 5 grade 2 and a trend towards more chronic GVHD in patients conditioned with the addition of anthracyclines. For all patients the risk for chronic GVHD, but not for acute GVHD, increased with a higher number of T cells in the graft. The projected 5-year probability of relapse was significantly lower in the group of patients conditioned with anthracyclines; 26% versus 52% (P ¼ 0 . 015). In multivariate analysis the addition of anthracyclines to the conditioning regimen was the only significant factor contributing to a lower probability of relapse. The projected 5-year probability of leukaemia-free survival [LFS] in the patients conditioned with and without the addition of anthracyclines was 56% and 36%, respectively (P ¼ 0 . 004). In multivariate analysis the addition of anthracyclines to the conditioning regimen correlated significantly with a lower number of mixed chimaeras in patients at 6 and 12 months after BMT. Mixed chimaerism at 6 months after transplantation did not significantly correlate with a higher incidence of relapse in further follow-up. In contrast, mixed chimaerism at 12 months after BMT was significantly associated with higher relapse rate.We conclude that the addition of anthracyclines to the conditioning regimen improves outcome of BMT using Tcell-depleted grafts.

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Section: Discussionsupporting

confidence: 91%

Outcome of transplantation for standard‐risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen

Schaap¹,

Schattenberg²,

Bär³

et al. 1997

Br J Haematol

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“…The development of molecular techniques to quantify chimaerism, has shed new light on the kinetics of T-cell and myeloid cell engraftment. Persisting mixed chimaerism after SCT has been associated with relapse in some, but not all studies (Petz et al, 1987;Bertheas et al, 1988;Schattenberg et al, 1989;Offit et al, 1990;Schaap et al, 1997;Schaap et al, 2002). However, these investigators evaluated only whole blood chimaerism, and as a consequence, little is known about lineage-specific donor engraftment -especially in the context of myeloablative TCD transplants.…”

Section: Discussionmentioning

confidence: 99%

Lineage‐specific engraftment and outcomes after T‐cell‐depleted peripheral blood stem cell transplant with Flu/Cy/TBI conditioning

Montero

Savani

Kurlander³

et al. 2005

Br J Haematol

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Allogeneic stem cell transplantation (SCT) continues to provide the best chance of cure for selected patients with haematological malignancies. However, transplant-related mortality (TRM) and graft-versus-host disease (GVHD) offset the unique therapeutic advantage of the graft-versus-leukaemia (GVL) effect. Although T-cell-depleted (TCD) SCT results in lower TRM and GVHD rates, the disease-free survival is comparable with that of unmanipulated SCT because of a higher rate of disease relapse and graft rejection (Marmont et al, 1991). To offset these disadvantages, while conserving the beneficial effect of T-cell depletion, we have used a myeloablative TCD peripheral blood stem cell transplant (PBSCT) followed by a transfusion of donor lymphocytes (DLI) after a delay of 45-100 d. The rationale of this approach was to boost T-cell immunity while mitigating GVHD with the delayed lymphocyte infusion (Barrett et al, 1998). Several studies have drawn attention to the frequent occurrence of mixed haematopoietic chimaerism after TCD transplants and have linked relapse and unfavourable transplant outcome with the mixed chimaeric state (Walker et al, 1986;Schaap et al, 1997;Bader et al, 1998;Barrios et al, 2003;Lamba et al, 2004). However, the relative patterns of engraftment of T-cells and myeloid cells have not been well described after these myeloablative SCT. We therefore evaluated donor T-cell and myeloid chimaerism in our hybrid T-cell depletion and add-back protocol, correlating chimaerism results with transplant outcomes. T lymphocyte (CD3 + cells) and myeloid (CD14 + /CD15 + cells) lineage specific chimaerism was measured regularly in the first 3 months post-transplant. Here we describe factors associated with mixed chimaerism, and the relationship between early mixed chimaerism and transplant outcome in patients with haematological malignancies receiving TCD human leucocyte antigen (HLA)-identical PBSCT and delayed DLI. SummarySixty patients with haematological malignancies received a myeloablative regimen of total body irradiation, cyclophosphamide and fludarabine followed by a T-cell-depleted peripheral blood stem cell transplant from a human leucocyte antigen identical sibling. To improve donor immune function, 1 · 10 7 CD3 + cells/kg were added-back between d 45 and 100. Tcell and myeloid chimaerism were monitored regularly to evaluate the effect of T-cell chimaerism on outcome. The major factor affecting outcome was disease risk, with significantly lower relapse and higher survival in 29 standard risk (SR) patients compared with 31 patients at high risk (HR) for treatment failure (relapse 4AE8 ± 5% vs. 59 ± 11%, P < 0AE0001, and overall survival 93 ± 5% vs. 39 ± 10%, P < 0AE0001, respectively). Donor myeloid chimaerism reached ‡95% within 14 d of transplant, but in the first several months, donor T-cell chimaerism was frequently mixed. Full T-cell chimaerism was significantly more frequent in HR vs. SR patients. Landmark analysis at days 30 and 90 in HR patients with mixed versus full T-cell chimaerism, sho...

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“…Results are available within 6 h, enabling informed clinical decisions to be made within the same working day. Many methods have been developed to evaluate chimaeric status after allogeneic BMT (Blazer et al, 1985;Bertheas et al, 1988;Leclair et al, 1995). Problems of specificity, sample size and complex methodology have meant that these methods have mainly now been superseded by microsatellite PCR analyses (Lawler et al, 1989;Roth et al, 1990;Roy et al, 1990;Roux et al, 1992;MacKinnon et al, 1994;Molloy et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Same‐day determination of chimaeric status in the immediate period following allogeneic bone marrow transplantation

et al. 1997

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Summary. The accurate and rapid determination of the origin of haemopoietic cells may provide valuable information as to the aetiology of, and most appropriate therapy for, leucopenia following allogeneic bone marrow or peripheral blood stem cell transplantation. We describe an approach to the analysis of chimaerism post bone marrow transplantation (BMT) based on the immunomagnetic capture of white cells combined with microsatellite polymerase chain reaction (PCR) and resolution of products by polyacrylamide gel electrophoresis (PAGE). This non-isotopic method enables the chimaeric status to be determined from as little as 1 . 0 ml of profoundly leucopenic peripheral blood (WBC р0 . 1 × 10 9 /l) and has been applicable to all donor/recipient pairs tested so far. Results are available within 6 h of blood sampling and lineage-specific chimaerism is possible. Furthermore, blood transfusions do not interfere with the analysis.

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

Cited by 46 publications

References 0 publications

Outcome of transplantation for standard‐risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen

Outcome of transplantation for standard‐risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen

Lineage‐specific engraftment and outcomes after T‐cell‐depleted peripheral blood stem cell transplant with Flu/Cy/TBI conditioning

Same‐day determination of chimaeric status in the immediate period following allogeneic bone marrow transplantation

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