Polyclonal primitive hematopoietic progenitors can be detected in mobilized peripheral blood from patients with high-risk myelodysplastic syndromes

Delforge, Michel; Demuynck, Hilde; Vandenberghe, Peter; Verhoef, Gregor; Zachée, Pierre; Duppen, Van; Marijnen, P; Berghe, Herman Van den; Boogaerts, M. A.

doi:10.1182/blood.v86.10.3660.bloodjournal86103660

Cited by 69 publications

(23 citation statements)

References 33 publications

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“…Three patients with a normal to excellent PBPC yield (nos. 5, 6 and 9) were demonstrated to be polyclonal by techniques based on X-chromosome inactivation (PCR analysis with the HUMARA probe) (Delforge et al, 1995). Other investigators confirmed in in vitro experiments, using the same X-linked probe, the possibility to culture polyclonal progenitors in patients with established MDS (Anan et al, 1995).…”

Section: Discussionmentioning

confidence: 84%

Feasibility of peripheral blood progenitor cell harvest and transplantation in patients with poor‐risk myelodysplastic syndromes

Demuynck¹,

Delforge²,

Verhoef³

et al. 1996

Br J Haematol

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Myelodysplastic syndromes (MDS) are a group of clonal haematological disorders with a highly unfavourable prognosis. Allogeneic bone marrow transplantation offers the sole possibility for cure and prolonged survival, but is only available for a minority of patients. Therefore, we investigated the feasibility of PBPC collection and transplantation in 11 patients with high-risk myelodysplasia who were not eligible for allogeneic bone marrow transplantation. In six patients, PBPC were harvested after mobilization with G-CSF alone. Five patients were harvested during the recovery phase of intensive chemotherapy combined with G-CSF. This resulted in seven patients in an adequate CD34 progenitor yield > 1 x 10(6)/kg. Six patients obtained a CFU-GM content of the PBPC harvest > 10 x 10(4)/kg. Five patients were subsequently transplanted following a standard BuCy4 regimen. The median to ANC (absolute neutrophil count) > or = 0.5 and 1.0 x 10(9)/l was respectively 14 d (range 10-18) and 16 d (range 11-25). Platelets were self-supporting > or = 20 x 10(9)/l after a median of 41 d (ranges 8-144). One patient had a persistent lack of platelet engraftment unresponsive to infusion of back-up bone marrow. These data demonstrate that in selected patients with high-risk MDS, adequate PBPC collection appears feasible, enabling the harvest of sufficient cell numbers required for rapid and stable engraftment after reinfusion. Improvement in mobilization efficiency may enable the collection of higher CD34+ progenitor cell numbers required for more rapid platelet engraftment. PBPC transplantation may be an alternative treatment option for patients who lack an allogeneic marrow donor. Follow-up is, however, still too limited to draw any conclusion regarding the long-term cure rate.

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Section: Discussionmentioning

confidence: 84%

Feasibility of peripheral blood progenitor cell harvest and transplantation in patients with poor‐risk myelodysplastic syndromes

Demuynck¹,

Delforge²,

Verhoef³

et al. 1996

Br J Haematol

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“…Chemotherapy induces cytogenetically normal CRs in the majority of patients (de Witte et al, 1995). In addition, the peripheral stem cell harvests of three patients with MDS appeared to be polyclonal, when assessed by polymerase chain reaction (PCR) techniques based on X-chromosome inactivation patterns (Delforge et al, 1995). Preliminary data indicate that repopulation after transplantation with mobilized peripheral stem cells was much faster than autologous bone marrow transplantation (Carella et al, 1996;Demuynck et al, 1996).…”

Section: Discussionmentioning

confidence: 98%

Haematopoietic stem cell transplantation for patients with myelo‐dysplastic syndromes and secondary acute myeloid leukaemias: a report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

Hermans²,

et al. 2000

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Summary. Allogeneic stem cell transplantation from an HLA-identical sibling donor is a curative treatment option for a young patient with myelodysplastic syndrome, limited by age and lack of sibling donors. Alternative stem cell sources have been used more recently, such as unrelated donors, non-identical family members or autologous transplants. This analysis of 1378 transplants reported to the European Group for Blood and Marrow Transplantation (EBMT) addresses the outcome of the varying procedures according to the known risk factors. The estimated diseasefree survival (DFS) and estimated relapse risk at 3 years were both 36% for 885 patients transplanted with stem cells from matched siblings. In the multivariate analysis, age and stage of disease had independent prognostic significance for DFS, survival and treatment-related mortality. Patients transplanted at an early stage of disease had a significantly lower risk of relapse than patients transplanted at more advanced stages. The estimated DFS at 3 years was 25% for the 198 patients with voluntary unrelated donors, 28% for the 91 patients with alternative family donors and 33% for the 126 patients autografted in first complete remission. The nonrelapse mortality was 58% for patients with unrelated donors, 66% for patients with non-identical family donors and 25% for autografted patients. The relapse rate of 18% was relatively low for patients with non-identical family donors, 41% for patients with unrelated donors and 55% for patients treated with autologous stem cell transplantation. Both allogeneic and autologous stem cell transplantation have emerged as treatment options for patients with myelodysplastic syndromes. Transplantation with an HLA-identical sibling donor is the preferred treatment option. Patients without an HLA-identical sibling donor may be treated with either autologous stem cell transplantation or an alternative donor transplantation. Patients younger than 20 years may be treated with an unrelated donor transplantation. Patients older than 40 years, and probably also patients between 20 and 40 years, may benefit most from an autologous stem cell transplantation.

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“…Mobilization of peripheral blood stem cells (PBSC) offers an alternative in such cases. Furthermore, peripheral stem cell transplants in MDS patients are capable of restoring sustained polyclonal haemopoiesis after high-dose chemotherapy (Delforge et al, 1995;Demuynck et al, 1996), and offer the additional potential advantage of more rapid and complete haemopoietic reconstitution when compared to ABMT . Our study demonstrates the feasibility of stem cell collection and subsequent autologous transplantation following FLAG-idarubicin chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Fludarabine, cytarabine, G‐CSF and idarubicin (FLAG‐IDA) for the treatment of poor‐risk myelodysplastic syndromes and acute myeloid leukaemia

et al. 1997

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Nineteen patients with high‐risk myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) received fludarabine, cytarabine, granulocyte‐colony stimulating factor (G‐CSF), and idarubicin chemotherapy (de novo MDS/MDS‐AML, nine; relapsed/refractory MDS/AML, seven; therapy‐related MDS, three). Median age was 44 years and median disease duration 10 months. 16/19 (84%) patients had abnormal cytogenetics with seven (37%) harbouring abnormalities of chromosome 7. 18/19 (94.7%) patients responded to FLAG‐idarubicin with 12 (63%) achieving complete remission (CR) (<5% blasts and normal cytogenetics). 7/9 (78%) patients with de novo MDS/MDS‐AML achieved CR compared to 5/10 (50%) with alternative diagnoses. Response was associated with age < 50 years, disease duration < 3 months, and cytogenetics other than abnormalities of chromosome 7. Haemopoietic regeneration was rapid in most patients and there were no toxic deaths. Nine patients received a second course of chemotherapy, three have proceeded to allogeneic bone marrow transplant and three to autologous blood stem cell/bone marrow transplantation. Follow‐up is short (median 10 months). 12/19 (63%) patients remain alive and 5/12 (42%) have relapsed at a median 5 months following CR achievement. FLAG‐idarubicin was well tolerated. High rates of morphological and cytogenetic remission, especially in de novo MDS, offer a window of opportunity for assessment of autologous BMT in this group of diseases where no treatment except alloBMT has led to prolongation of survival.

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Polyclonal primitive hematopoietic progenitors can be detected in mobilized peripheral blood from patients with high-risk myelodysplastic syndromes

Cited by 69 publications

References 33 publications

Feasibility of peripheral blood progenitor cell harvest and transplantation in patients with poor‐risk myelodysplastic syndromes

Feasibility of peripheral blood progenitor cell harvest and transplantation in patients with poor‐risk myelodysplastic syndromes

Haematopoietic stem cell transplantation for patients with myelo‐dysplastic syndromes and secondary acute myeloid leukaemias: a report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

Fludarabine, cytarabine, G‐CSF and idarubicin (FLAG‐IDA) for the treatment of poor‐risk myelodysplastic syndromes and acute myeloid leukaemia

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