scispace - formally typeset
Search or ask a question

Showing papers by "Eliane Gluckman published in 1998"


Journal ArticleDOI
TL;DR: Cord blood is a feasible alternative source of hematopoietic stem cells for pediatric and some adult patients with major hematologic disorders, particularly if the donor and the recipient are related.
Abstract: Background Cord-blood banks have increased the use of cord-blood transplantation in patients with hematologic disorders. We have established a registry containing information on the outcome of cord-blood transplantation. Methods We sent questionnaires to 45 transplantation centers for information on patients receiving cord-blood transplants from 1988 to 1996. Reports on 143 transplantations, performed at 45 centers, were studied, and the responses were analyzed separately according to whether the donor was related or unrelated to the recipient. Results Among 78 recipients of cord blood from related donors, the Kaplan–Meier estimate of survival at one year was 63 percent. Younger age, lower weight, transplants from HLA-identical donors, and cytomegalovirus-negative serologic results in the recipient were favorable prognostic factors. Graft-versus-host disease of at least grade II occurred at estimated rates of 9 percent in 60 recipients of HLA-matched cord blood and 50 percent in 18 recipients of HLA-misma...

480 citations


Journal ArticleDOI
TL;DR: PBPC donors tolerated filgrastim administration and leukapheresis well with the most frequent side-effects being musculoskeletal pain, headache, and mild increases of LDH, AP, Gamma-GT or SGPT; the number of days with restricted activity and of nights spent in hospital was lower in donors of PBPC.
Abstract: In a multicentre trial involving 20 transplant centres from 10 countries haematopoietic stem cells were obtained either from the bone marrow of 33 sibling donors or from the peripheral blood of 33 such donors after administration of filgrastim (10 μg/kg/day). The haematopoietic stem cells were infused into their HLA-identical recipients suffering from acute leukaemias in remission or chronic myeloid leukaemia in chronic phase. PBPC donors tolerated filgrastim administration and leukapheresis well with the most frequent side-effects being musculoskeletal pain, headache, and mild increases of LDH, AP, Gamma-GT or SGPT. Pain and haematoma at the harvest site and mild anaemia were the most frequent complaints of BM donors. Severe or life-threatening complications were not seen with any type of harvest procedure. Time to platelet recovery greater than 20 × 109/l was 15 days (95% confidence interval (CI) 13–16 days) in the PBPCT group and 19 days (CI 16–25) in the BMT group. Time to neutrophil recovery greater than 0.5 × 109/l was 14 days (CI 12–15 days) in the PBPCT group as compared to 15 days (CI 15–16 days) in the BMT group. The numbers of platelet transfusions administered to PBPCT and BMT patients were 12 (range: 1–28) and 10 (range: 3–39), respectively. Sixteen patients (48%) transplanted with bone marrow and 18 patients (54%) transplanted with PBPC developed acute GVHD of grades II–IV; acute GVHD of grades III or IV developed in six (18%) and seven (21%) patients, respectively. Kaplan–Meier plots for transplant-related mortality until day 100 and leukaemia-free survival at a median of 400 days after BMT or PBPCT showed no significant differences. Administration of filgrastim and leukapheresis in normal donors were feasible and well tolerated. The number of days with restricted activity and of nights spent in hospital was lower in donors of PBPC. Transplantation of PBPC to HLA-identical siblings with early leukaemia resulted in earlier platelet engraftment. The incidence of moderate to severe acute GVHD, transplant-related mortality, and leukaemia-free survival did not show striking differences. Further investigation of allogeneic PBPCT as a substitute for allogeneic BMT is warranted.

266 citations


Journal ArticleDOI
TL;DR: The characteristics of the environmental fungal population explains the two main results obtained from the typing of the clinical isolates: the absence of a common strain responsible for an invasive aspergillosis outbreak results from the extreme diversity of theEnvironmental population of A. fumigatus in contact with the patients.
Abstract: Fingerprinting of more than 700 clinical and environmental isolates of Aspergillus fumigatus from four differential hospital settings was undertaken with a dispersed repeated DNA sequence. The analysis of the environmental isolates showed that the airborne A. fumigatus population is extremely diverse, with 85% of the strains being represented as a single genotype isolated once. The remaining 15% of the strains were isolated several times and were able to persist for several months in the same hospital environment. No strains were found to be associated with a specific location inside the hospital, and identical strains were isolated from different buildings of the hospital and outdoors. Isolation of the same strain both from patients and from the environment of the same hospital is highly suggestive of a nosocomial infection. The characteristics of the environmental fungal population explains the two main results obtained from the typing of the clinical isolates: (i) the absence of a common strain responsible for an invasive aspergillosis outbreak results from the extreme diversity of the environmental population of A. fumigatus in contact with the patients, and (ii) patients hospitalized in different wards of the same hospital can be infected with the same strain since every patient might inhale the same spore population.

199 citations


Journal ArticleDOI
TL;DR: The high incidence of BM failure in association with a wide range of somatic abnormalities together with the ubiquitous expression of DKC1 suggest that, as well as having a critical role innormal haemopoiesis, this gene has a key role in normal cell biology.
Abstract: Dyskeratosis congenita (DC) is an inherited disorder characterized by skin pigmentation, nail dystrophy and mucosal leucoplakia. In 1995 a Dyskeratosis Congenita Registry was established at the Hammersmith Hospital. In the 46 families recruited, 76/83 patients were male, suggesting that the major form of DC is X-linked. As well as a variety of noncutaneous abnormalities, the majority (93%) of patients had bone marrow (BM) failure and this was the principal cause (71%) of early mortality. In addition to BM hypoplasia, some patients also developed myelodysplasia and acute myelod leukaemia. Pulmonary abnormalities were present in 19% of patients. In affected females the phenotype was less severe. Some female carriers of X-linked DC had clinical features. Carriers of X-linked DC showed skewed X-chromosome inactivation patterns (XCIPs), suggesting that cells expressing the normal DC allele have a growth/survival advantage over cells that express the mutant allele. Linkage analysis in multiplex families confirmed that the DKC1 gene, responsible for the X-linked form of DC, is located within Xq28 and facilitated its positional cloning. The high incidence of BM failure in association with a wide range of somatic abnormalities together with the ubiquitous expression of DKC1 suggest that, as well as having a critical role in normal haemopoiesis, this gene has a key role in normal cell biology.

175 citations


Journal ArticleDOI
TL;DR: The most important long‐term complication was the occurrence of cancer in seven patients (8‐year projected incidence 24%) and growth retardation was common, whereas late complications were rare.
Abstract: We describe the long-term follow-up of 50 Fanconi's anaemia patients who were transplanted from a related donor with a median follow-up of >6 years The survival estimate was 744% at 54 months and 585% at 100 months All patients were conditioned with low-dose cyclophosphamide and thoraco-abdominal irradiation Acute graft-versus-host disease (GvHD) of grade II or more developed in 26 patients and chronic GvHD developed in 30/43 (699%) patients The survival of patients without chronic GvHD (n = 13) was 100% In addition to chronic GvHD, 20 pre-transplant transfusions was shown to have an adverse impact on survival by multivariate analysis (relative risk = 708, P = 00003) Prospective follow-up of growth and endocrine function could be performed in 31 patients Of 20 boys, six have already reached normal puberty within the expected time Among the 11 girls, three were at the pubertal age at the time of analysis Growth retardation was common, whereas late complications (eg peripheral hypothyroidism, cataract) were rare However, the most important long-term complication was the occurrence of cancer in seven patients (8-year projected incidence 24%) Among the 32 survivors, 27 (845%) had a normal and four a moderately reduced performance status, and all achieved complete engraftment with donor cells Therefore transplantation was able to cure these patients who remain at high risk for developing late complications Clearly, a genetic predisposition and chronic GvHD could have led to the development of these cancers However, we cannot completely rule out irradiation as a cofactor in the genesis of these cancers, and therefore no longer use irradiation for the conditioning of Fanconi's anaemia patients

118 citations


Journal ArticleDOI
TL;DR: Five boys transplanted with an HLA‐identical related donor for severe aplastic anaemia associated with Dyskeratosis congenita are reported; in all cases successful engraftment was observed.
Abstract: Dyskeratosis congenita (DC) is a rare inherited disorder often associated with aplastic anaemia. We report the cases of five boys transplanted with an HLA-identical related donor for severe aplastic anaemia (SAA) associated to DC; in all cases successful engraftment was observed. Three patients died 2-8 years after bone marrow transplantation (BMT) with signs of endothelial cell damage syndrome (kidney microangiopathy and liver veno-occlusive disease). Another boy died 1 year after BMT from Evans syndrome and invasive aspergillosis. One boy currently presents anaemia, polyarthritis of unknown origin, pulmonary fibrosis and gut malabsorption 7.5 years after BMT. SAA associated with DC can be successfully treated by allogeneic BMT. However, these early and late complications observed are very unusual after BMT and probably reflect the association of transplanted-related factors, evolution of the underlying disease, and increased sensitivity of endothelial cells. Modified conditioning approaches, advances in supportive care and surveillance of these unusual complications offer the possibility of improved outcome for these patients.

115 citations


Journal ArticleDOI
TL;DR: SCC developing in marrow transplant recipients seems to occur via a multistep process, and genetic predisposition may be present, as in patients with Fanconi's anemia.
Abstract: Background. Secondary solid tumors are rare events occurring in patients who underwent allogeneic marrow transplantation for aplastic anemia and Fanconi's anemia. Human herpes virus 8 (HHV8), Epstein-Barr virus (EBV), and human papillomaviruses (HPV) sequences have been found in squamous cell carcinoma (SCC) occurring in organ transplant recipients. The tumor suppressor gene p53 has been strongly linked to the occurrence of SCC in the nonimmunocompromised population. Patients and methods. In eight patients with SCC, we searched for HHV8, EBV, varicella zoster virus, adenovirus, and HPV sequences from DNA extracted from selected areas of SCC. We also looked for p53 expression in those specimens as well as the presence of anti-p53 antibodies in the serum of these patients at the onset of SCC. Results. In one patient, we found the presence of both HHV8 and EBV sequences, and in another patient we found HPV16 sequences. All five tumors that could be studied disclosed evidence of p53 accumulation, but none of the eight patients had anti-p53 antibodies in the sera. Conclusion, SCC developing in marrow transplant recipients seems to occur via a multistep process. Genetic predisposition may be present, as in patients with Fanconi's anemia. Transplantation-related factors, such as irradiation and chronic graft-versus-host disease, also have a role. In this article, we add two more potent risk factors: p53 alteration(s) and in some cases the presence of oncogenic viruses.

56 citations


Journal Article
TL;DR: Results are in favor of freezing cord blood in families in whom a transplant might be indicated, and related cord blood transplantation offers a good alternative to BMT.
Abstract: Eurocord Transplant has established a registry for studying results of cord blood transplant. We have analyzed 78 patients who have received a related CBT between October 1988 and December 1996. The median follow-up time was 29 months (1-99). The median age was 5 years (0.2-20), median weight 19 kg (5-50). Forty-six patients had a malignant disease: 32 acute leukemia (AL), six chronic myeloid leukemia (CML), four myelodysplastic syndrome, two neuroblastoma and two non-Hodgkin lymphoma. Thirty-two patients were transplanted for non-malignant diseases including 17 bone marrow failure syndromes (BMFS), three sickle cell anemia, five thalassemia and seven inborn errors. The donor was an HLA-identical sibling in 60 cases and an HLA-mismatched donor in 18 cases. As conditioning, 36 patients received irradiation and 40 patients received associated busulfan-containing regimens. GVHD prophylaxis consisted of CsA alone in 36 cases, CsA associated with prednisone in eight cases, CsA, methotrexate (Mtx) with or without prednisone in 28 cases and CsA with monoclonal antibody or ATG in four cases. The median number of nucleated cells (NC) infused/kg was 3.9 x 10(7) (0.7-15). One-year survival was 63 +/- 6%. Age, weight, HLA identity and negative cytomegalovirus (CMV) serology in the recipient were significant favorable prognostic factors. Among these 78 patients, the incidence of grade > or = II GVHD was 9% in HLA-matched CBT and 50% in mismatched CBT (P < 0.001). Neutrophil engraftment was associated with age <6 years (P = 0.02) and weight <20 kg (P = 0.02). It was 73% in patients receiving <3.7 x 10(7) nucleated cells (NC) infused/kg and 85% in patients receiving more (P = 0.06). Favorable factors for platelets engraftment were age <6 years (P = 0.03), weight <20 kg (P = 0.002) and HLA identity (P < 0.0001). Related cord blood transplantation offers a good alternative to BMT. Theses results are in favor of freezing cord blood in families in whom a transplant might be indicated.

43 citations


Journal ArticleDOI
TL;DR: It is shown that cord blood is an alternative source of hematopoietic stem cells for allogeneic transplantation in children and in some adults and the number of cells infused is important and the use of a number of nucleated cells inferior to lx107/kg is not recommended.
Abstract: Allogeneic haematopoietic stem cell transplantation (HSCT) has been used to treat thousands of patients, adults and children, with life-threatening haemato-logical diseases. The principal limitations of allogeneic bone marrow transplantation are the lack of suitable HLA-matched donors and the complications of graft-versus-host disease associated with HLA disparities. In the absence of a suitable HLA identical sibling donor, alternative donors such as mismatched related or matched unrelated donors are searched. In these transplants, major and minor histocompatibility differences are often unrecognised by current matching tests, explaining the relatively high frequency of post transplant complications, graft failure, graft-versus-host disease and delayed immune reconstitution. The description of new more sensitive techniques of typing by molecular biology and has decreased the probability of finding a fully matched donor. Despite a bone marrow donor registry which contains more than 4 millions bone marrow donors world-wide, some patients cannot be transplanted because of the lack of an HLA identical donor.

38 citations


01 Jan 1998
TL;DR: In the absence of a suitable HLA identical sibling donor, alternative donors such as mismatched related or matched unrelated donors are searched as discussed by the authors, which explains the relatively high frequency of post transplant complications, graft failure, graft-versus-host disease and delayed immune reconstitution.
Abstract: Allogeneic haematopoietic stem cell transplantation (HSCT) has been used to treat thousands of patients, adults and children, with life-threatening haemato-logical diseases. The principal limitations of allogeneic bone marrow transplantation are the lack of suitable HLA-matched donors and the complications of graft-versus-host disease associated with HLA disparities. In the absence of a suitable HLA identical sibling donor, alternative donors such as mismatched related or matched unrelated donors are searched. In these transplants, major and minor histocompatibility differences are often unrecognised by current matching tests, explaining the relatively high frequency of post transplant complications, graft failure, graft-versus-host disease and delayed immune reconstitution. The description of new more sensitive techniques of typing by molecular biology and has decreased the probability of finding a fully matched donor. Despite a bone marrow donor registry which contains more than 4 millions bone marrow donors world-wide, some patients cannot be transplanted because of the lack of an HLA identical donor.

34 citations




Journal Article
TL;DR: Despite a short follow-up and the small number of patients analysed, transplants using HLA matched family cord blood give some promising results, but first results with unrelated cord blood remind that this approach is clearly an experimental one that has to be evaluated through international registries and prospective studies.
Abstract: Fanconi anaemia is a hereditary disorder characterised by chromosomal breaks increased by cross-linking agents. Bone marrow transplantation is the treatment of choice when a HLA identical sibling donor has been identified. The use of low-dose cyclophosphamide with thoraco-abdominal irradiation for the conditioning regimen of FA patients has lead to a dramatic improvement of survival, with a long-term survival of 75% at our institution. However, if most patients are completely cured of their haematological disease, there is concern about an increased frequency of secondary tumours, mostly head and neck squamous cell carcinomas of poor prognosis. Results of BMT using alternative donors (HLA mismatched related and unrelated donors) have also improved during the last decade. A better selection of the donor via high-resolution techniques for class-II HLA matching, and more recently the use of T cell depleted grafts are probably the main explanations. Despite a short follow-up and the small number of patients analysed, transplants using HLA matched family cord blood give some promising results. On the other hand, first results with unrelated cord blood remind that this approach is clearly an experimental one that has to be evaluated through international registries and prospective studies. New approaches including autologous stem cell transplantations and gene therapy are currently explored.

Journal Article
TL;DR: The EUROCORD experience of 10 patients transplanted with related cord blood for hemoglobinopathies with beta-thalassemia and sickle cell anemia is reported on.
Abstract: Patients with beta-thalassemia (Hbeta th) and sickle cell anemia (SCA) can be treated with bone marrow transplantation. Stem cells from cord blood have several theoretical advantages, however, the place of cord blood transplant for hemoglobinopathies has not yet been established. We report here the EUROCORD experience of 10 patients (Hbeta th = 7, SCA = 3) transplanted with related cord blood.


Journal Article
TL;DR: Despite a short follow-up and the small number of patients analysed, transplants using HLA matched family cord blood give some promising results, but first results with unrelated cord blood remind that this approach is clearly an experimental one that has to be evaluated through international registries and prospective studies.
Abstract: Fanconi anaemia is a hereditary disorder characterised by chromosomal breaks increased by cross-linking agents. Bone marrow transplantation is the treatment of choice when a HLA identical sibling donor has been identified. The use of low-dose cyclophosphamide with thoraco-abdominal irradiation for the conditioning regimen of FA patients has lead to a dramatic improvement of survival, with a long-term survival of 75% at our institution. However, if most patients are completely cured of their haematological disease, there is concern about an-increased frequency of secondary tumours, mostly head and neck squamous cell carcinomas of poor prognosis. Results of BMT using alternative donors (HLA mismatched related and unrelated donors) have also.improved during the last decade. A better selection of the donor via high-resolution techniques for class-II HLA matching, and more recently the use of T cell depleted grafts are probably the main explanations. Despite a short follow-up and the small number of patients analysed, transplants using HLA matched family cord blood give some promising results. On the other hand, first results with unrelated cord blood remind that this approach is clearly an experimental one that has to be evaluated through international registries and prospective studies. New approaches including autologous stem cell transplantations and gene therapy are currently explored.

Journal Article
TL;DR: In this article, the outcome of cord blood transplants (CBT) was analyzed for survival, engraftment and graft-versus-host disease (GVHD) for patients with hematological disorders.
Abstract: Cord blood banks have increased the use of cord blood transplants (CBT) for patients with hematological disorders. EUROCORD has established a registry for providing information on the outcome of CBT. Questionnaires were sent to all EUROCORD members to collect information on patients transplanted from 1988 to 1996. One hundred and forty-three CBT, performed in 45 centers, were analyzed for survival, engraftment and graft-versus-host disease (GVHD). Results in recipients of related and unrelated transplants were analyzed separately. In 78 patients who received CB from a related donor, 1-year survival was 63 +/- 6%. Age, weight, HLA identity and negative cytomegalovirus (CMV) serology in the recipient were significant favorable prognostic factors. Among these 78 patients, the incidence of grade > or = II GVHD was 9% in HLA matched CBT and 50% in mismatched CBT. Neutrophil engraftment was associated with age or = II was observed in 40% of these patients. Negative recipient CMV serology was the most important factor for predicting GVHD (P = 0.04). Neutrophil recovery was 76% in patients receiving < 3.7 x 10(7) NC/kg and 94% in patients receiving more (P = 0.008). Cord blood is a feasible alternative source of hematopoietic stem cells for treating patients with various hematological disorders.

Journal ArticleDOI
TL;DR: A case of Hodgkin's disease developing 8 years after allogeneic bone marrow transplantation for chronic myelogeneous leukemia is reported, which is of interest because of its donor origin and its association with Epstein-Barr virus infection.
Abstract: Secondary malignancies (lymphomas, leukemias, and solid tumors) occurring after bone marrow transplantation are now more frequently reported, as the patients surviving the early phase of the graft and remaining free of their original disease are more numerous. Besides early Epstein-Barr virus-associated B-cell lymphoproliferative diseases, which are the most common type and most often of donor origin, few late-occurring lymphomas have been described that might represent a distinct entity. We report here a case of Hodgkin's disease developing 8 years after allogeneic bone marrow transplantation for chronic myelogeneous leukemia. Only two Hodgkin's diseases after allogeneic bone marrow transplantation have been reported in the literature so far. The case we report is of interest because of its donor origin and its association with Epstein-Barr virus infection.

Journal ArticleDOI
TL;DR: The study of the specific features of the osteonecrosis may lead to the recommendation of primary total hip arthroplasty after failure of the medical treatment, and there was no significant difference between the Ficat grades, except for Grade 0, which showed a higher survival rate.
Abstract: Thirty-five patients with bilateral osteonecrosis of the femoral head after bone marrow transplantation were reviewed retrospectively. The median age at the time of transplantation was 26 years. The first symptoms occurred within 2 years of transplantation. At presentation, 18 of the patients reported pain in both hips, 17 had symmetric radiographic lesions, and 39 of the hips had collapsed. Medical treatment was indicated initially. At the final examination before surgery (median, 3.5 years), 31 patients had bilateral hip pain, 22 patients had symmetric radiographic lesions, and 56 of the hips had collapsed. Fifty-seven of the hips required surgery, including one open drainage, four core decompressions, six cup arthroplasties, and 46 primary total hip replacements. Six hips (four core decompressions; two cups) later underwent total hip replacement revision, and a deep infection developed in one. By considering the requirement of a total hip replacement as a failure of conservative treatment, the rate of survival of the femoral head was 30% 5 years after the transplant. There was no significant difference between the Ficat grades, except for Grade 0, which showed a higher survival rate. The study of the specific features of the osteonecrosis may lead to the recommendation of primary total hip arthroplasty after failure of the medical treatment.

Journal Article
TL;DR: These results were similar to other series reported in the USA and showed the benefit of using mismatched unrelated cord blood in clearly defined situations.
Abstract: This report summarizes the results of unrelated cord blood transplants. Sixty-five patients were reported to Eurocord. One year survival was 29%. Factors associated with survival were diagnosis, inborn errors had a better survival than leukemia or aplastic anemia; higher number of cells infused and negative pre-transplant CMV serology were also favorable factors. Granulocyte and platelet engraftment were associated with a higher number of nucleated cells infused, GVH incidence was low especially in CMV negative patients, it was not associated with the degree of HLA disparity. These results were similar to other series reported in the USA and showed the benefit of using mismatched unrelated cord blood in clearly defined situations.

Journal ArticleDOI
01 Sep 1998-Leukemia
TL;DR: This study highlights the strong influence of graft manipulation on the incidence of mixed chimaerism after transplantation from an unrelated donor and investigates the residual disease post-transplant.
Abstract: Marrow transplantation from unrelated donors has been linked with an increased risk of graft-versus-host disease (GVHD). In an attempt to lower the risk of acute GVHD we used CD34 marrow cell selection for T cell depletion. Since T cell depletion has been linked to an increased risk of relapse and an increased risk of marrow failure, we used PCR amplification of minisatellite sequences to investigate donor cell engraftment and RT-PCR amplification of recurrent chromosomal translocations to investigate the residual disease post-transplant. Twenty-three patients who underwent BMT after positive selection of the CD34-positive cell population were studied. Results were then compared with those of 37 patients who underwent transplantation with unmanipulated marrow graft. Among the 23 patients who received CD34+ selected cell grafts, seven (30%) had evidence of full donor engraftment, 14 had evidence of residual recipient cells (61%), one had a non-take, and one autologous bone marrow recovery. Analysis of the chimaerism status post-transplant in 36 patients who received unmanipulated marrow grafts showed that 31 patients (86%) had evidence of full donor engraftment. The difference in the incidence of mixed chimaerism profile between patients who received unmanipulated marrow graft and those receiving CD34+ selected cell grafts was statistically significant (P < 0.01). nine patients who received cd34+ selected cell grafts could be analysed for the presence of minimal residual disease post-transplant (one with t(9;22) acute lymphoblastic leukaemia and eight with CML). In the patient transplanted for a Ph-positive acute leukaemia, and in two out of the eight patients with CML, the search fora fusion transcript was consistently negative after transplantation. Among the six patients with evidence of residual disease, three patients also had a mixed chimaerism profile and were given donor lymphocyte infusions. Minimal residual disease study was performed post-transplant in 16 patients who received unmanipulated marrow grafts. In 10 of 14 patients with CML, and in two patients with acute leukaemia the search for a fusion transcript was consistently negative after transplantation. The difference in the incidence of minimal residual disease between patients who received an unmanipulated marrow graft and those receiving CD34+ selected cell grafts was not statistically significantly significant, but numbers of patients included in this analysis are still few. In conclusion, our study highlights the strong influence of graft manipulation on the incidence of mixed chimaerism after transplantation from an unrelated donor.

Journal ArticleDOI
TL;DR: It is described two cases of meningiomas developing 13 and 15 years after the graft, and it is important to consider the diagnosis ofMeningioma in long-term survivors presenting with neurological symptoms.
Abstract: Late complications occurring after allogeneic bone marrow transplant (BMT) are increasingly reported, since more patients survive. Among these late complications, solid tumors are of particular clinical concern. Only malignant brain tumors have been reported (astrocytoma, glioblastoma). We describe two cases of meningiomas developing 13 and 15 years after the graft. Occurrence of such benign tumors has been described after treatment of ALL, but not following allogeneic BMT. It is important to consider the diagnosis of meningioma in long-term survivors presenting with neurological symptoms.

Journal Article
TL;DR: Data confirm that allogeneic CBT from either a related or an unrelated donor is a feasible procedure able to cure a significant proportion of children with acute leukemia, especially if transplanted in a favorable phase of disease.
Abstract: Over the past decade, allogeneic cord blood transplantation (CBT) has been widely used for treating patients with malignant disorders. However, the reported low incidence of GVHD observed after allogeneic CBT might be a major drawback in leukemic recipients and at present it is not clear whether CBT really predisposes patients to an increased risk of leukemia relapse. In order to further elucidate the role of CBT in children with hematological malignancies, 54 patients with ALL or AML given either a related (31 cases) or an unrelated (23 cases) CBT in 25 centers participating in the Eurocord Registry were analyzed. Overall survival of related and unrelated CBT recipients was substantially similar, the most important factor influencing patients' outcome being disease state at time of transplantation. In fact, due to a markedly increased relapse rate, poor-risk children (ie patients transplanted in more advanced disease) experienced a significantly worse EFS than those given CBT in a more favorable disease phase (ie CR1 or CR2). These data confirm that allogeneic CBT from either a related or an unrelated donor is a feasible procedure able to cure a significant proportion of children with acute leukemia, especially if transplanted in a favorable phase of disease.



Journal Article
TL;DR: The Vbeta T cell cord blood repertoire is analyzed and only the overexpression of three Vbeta families are found: Vbeta 5-1, V beta 5-2, Vbeta 21-2.
Abstract: Umbilical cord blood T cells are less functional. Different explanations have been proposed. In this study we analyze the Vbeta T cell cord blood repertoire. All the Vbeta families are expressed. We found only the overexpression of three Vbeta: Vbeta 5-1, Vbeta 5-2, Vbeta 21-2.

Journal ArticleDOI
TL;DR: It is shown that AY19 mAb is reactive with 50-60% of the CD34+ cord blood cells and exhibits agonistic properties by inducing a significant increase in the size of CFU-GM colonies when added to serum-free liquid cultures of hematopoietic progenitors.
Abstract: AY19, a unique mAb was used to better characterize the umbilical cord blood hematopoietic progenitor subpopulations. This mAb identifies an 85 kDa cell surface glycoprotein. In this present study we showed that AY19 mAb is reactive with 50–60% of the CD34+ cord blood cells. Extensive phenotypical studies revealed that AY19 mAb defines a novel CD34+ subset different from the ones defined by anti-CD90, anti-CD38, anti-CD33, anti-CD71, anti-CD19, anti-CD7 or anti-HLA-DR mAbs. We show that AY19 mAb reacts with both primitive and committed progenitors including my-eloid and lymphoid progenitors. In addition, sorted CD34+high/AY19+ cells contain an increased number of CFU-GM and a decreased number of BFU-E compared with sorted CD34+high/AY19— cells. We show that AY19 mAb exhibits agonistic properties by inducing a significant increase in the size of CFU-GM colonies when added to serum-free liquid cultures of hematopoietic progenitors. This suggests that AY19 mAb identifies a cell surface receptor which may be involved in the regulation of hematopoietic cell proliferation.