Guy Cornu

Persistence of fetal hemoglobin production after successful transplantation of cord blood stem cells in a patient with sickle cell anemia.

A girl with sickle cell anemia was treated with cord blood transplantation combined with hematopoietic growth factor. Cord blood cells were collected from a sister with an identical human leukocyte antigen complex who was a carrier of the sickle cell trait (hemoglobin AS). The patient had complete engraftment and no graft-versus-host disease. The persistence of a high level of fetal hemoglobin 6 months after engraftment was noted.

Intracellular cytokine profile of cord and adult blood monocytes.

Cord blood (CB) transplantations are associated with low graft-versus-host disease (GVHD). The pathophysiology of GVHD involves interaction and activation of different cell types, as lymphocytes and monocytes, and results in a cascade of cytokine production. After antigen or mitogen stimulation, CB monocytes release lower levels of cytokines than adult blood (AB) monocytes. In this study, the detection of intracellular IL-1β and TNF-α produced by monocytes was evaluated in response to tuberculin PPD to investigate whether the reduced capacity of CB monocytes to secrete cytokines could be related to an impaired functional activity and to a particular phenotypic profile. Results showed that the percentage of CD64+monocytes producing intracellular IL-1β and TNF-α was significantly lower in CB and that the phenotypic profile of CB monocytes producing these cytokine (CD64+CD14+) was different to that of AB monocytes (CD64+CD14+, CD64+CD33+ and CD64+ CD45RO+). These results suggest that the lower capacity of CB monocyte populations to produce IL-1β and TNF-α might be due to a functional immaturity of CB monocytes at the cellular level as reflected by the different phenotypic profile of CB monocytes. Bone Marrow Transplantation (2001) 27, 1081–1086.

Expression of HLA-DR, CAM and co-stimulatory molecules on cord blood monocytes.

Abstract: Umbilical cord blood (CB) transplantations are associated with a lower risk of severe graft‐versus‐host disease (GVHD) compared to BMT. GVHD is an immune reaction that involves interaction between cell surface molecules resulting in cell activation and release of many cytokines. Monocytes are known to be an important source of cell adhesion (CAM) and co‐stimulatory molecules which play a crucial role in the efficient activation of T and B cells. We analyzed the phenotype of CB monocytes in the presence or absence of an inflammatory signal (rIFN‐γ) and compared them to adult blood (AB); the expression of HLA‐DR and 17 different markers (CD11a, CD11b, CD11c, CD18, CD29, CD40, CD44, CD49a, CD49d, CD49e, CD49f, CD54, CD58, CD62L, CD80, CD86 and CD102) was measured by flow cytometry. Statistical analysis showed that, compared to AB, CB monocytes did not express CD11b, CD11c, CD49d and after stimulation with rIFNγ, they lost the expression of CD58 and CD102, whereas CD80 and CD86 expression was induced. The analysis of fluorescence intensity (MFI) revealed that CB monocytes expressed some CAM (CD29, CD54, CD102) with a lower intensity than AB monocytes except CD44. In conclusion, absence and reduced expression of some markers argue for a different phenotypic profile of CB monocytes compared to AB monocytes, which might partly contribute to their impaired immune response and to the low incidence of GVHD observed after CB transplantations. However, CB monocytes expressed CD80 and CD86 co‐stimulatory molecules, but this expression did not prove a normal co‐stimulatory function.

Plasma infusion as treatment for 33 children with haemolytic uraemic syndrome: a good therapy?

Between May 87 and December 91, 33 children aged from 2 months to 13 9/12 years were admitted for haemolytic uraemic syndrome (HUS). Treatment consisted of daily fresh-frozen plasma infusion (20 ml/kg/day) during 14 days. On admission, 20 patients (61%) had an oligoanuria: 18 underwent a peritoneal dialysis and 2 an haemodialysis with a median duration of dialysis of 14 days. A good outcome was rapidly observed in all patients. A normalisation of the platelet count and a sustained normal level of haemoglobin were obtained after a median of 8 days. The follow-up ranged from 7 months to 4 8/12 years: all patients had a normal blood pressure with correct growth. Only 3 children (9%) still had urinary abnormalities: one an isolated microscopic haematuria 3 years after diagnosis and 2 others a mild proteinuria after 1 3/12 year and 4 8/12 years with reduction of the renal function to 80% of the normal for the last one. In our series, plasma infusions lead to a rapidly favourable outcome in all patients and seem to be an effective therapy of HUS in childhood.

Greffe de moelle dans l'anémie de Fanconi: à propos de sept cas

Objects.-Follow-up of patients with Fanconis anemia treated in our unit and review of the literature concerning bone marrow transplantation in Fanconis anemia. Patients and methods.-Ten patients were followed in our unit for 20 years. We summarize their clinical features, treatment and clinical course. Results.-Among the ten patients, seven received allogeneic marrow transplantation. Only two patients are still alive. Two transplanted patients died from complications shortly after the transplantation. Three other patients died later after the transplantation, two of them from oropharyngal carcinomas. Discussion.-The 5-year survival is about 70% in the transplantation with an HLA-identical sibling donor; it is only about 30% if the donor is an HLA-matched unrelated or mismatched related patient. Furthermore, retrospective studies have shown that the long-term outcome of carcinoma is a major complication after the transplantation. Conclusion.-Our series of patients with Fanconis anemia reflects fairly faithfully the complications encountered in this disease. Although the improvement of the graft technique may decrease the rate of death due to transplantation, the long-term development of solid tumors remains a problem for which no solution has been suggested up to now

Intermediate-risk childhood acute lymphoblastic leukemias: amsacrine + cytosine arabinoside versus intermediate-dose methotrexate for consolidation, and 6-mercaptopurine + methotrexate + vincristine versus monthly pulses for maintenance.

The prognosis for childhood acute lymphoblastic leukemia improved dramatically in the late 1970s, with 50%–70% of long-term survivors being reported following multiagent chemotherapy regimens. Unfortunately, the survival rate is still poor for relapsing patients.

Transplantation of umbilical cord blood in a refractory lymphoma.

A successful cord blood transplantation combined with hematopoietic growth factor was performed in a boy presenting with refractory mediastinal T-cell lymphoma. Cord blood cells were collected from an HLA-identical sibling at the time of delivery. A transient and corticosensitive acute grade II graft versus host disease was observed. One year after transplantation, the child is still in remission with complete engraftment. This is the first report of cord blood transplantation in a patient with refractory lymphoma.