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A Devergie

Publications and source records attributed to A Devergie.

At least 19 recordsLinked to original sources
PubMed2005

Late thyroid toxicity in 153 long-term survivors of allogeneic bone marrow transplantation for acute lymphoblastic leukaemia.

The purpose of this study was to identify risk factors for hypothyroidism after bone marrow transplantation (BMT) for high-risk or relapsed acute lymphoblastic leukaemia (ALL) in children. In all, 388 children with acute lymphoblastic leukaemia underwent allogeneic bone marrow transplantation between 1984 and 1994. Overall 5-year survival was 54.6%. Thyroid function was assessed in the 153 patients with more than 5 years of follow-up. In total, 16 patients developed uncompensated hypothyroidism (UH) and 46 compensated hypothyroidism (CH) a median of 2.9 and 2.7 years, respectively, after BMT. Thyroid dysfunction-free survival rates were 73.2% after 5 years and 59.2% after 10 years. Three factors were significantly associated with the onset of hypothyroidism, namely age, bone marrow transplantation in second remission, and single-dose total body irradiation (TBI). Ultrasonography of the thyroid showed nodules in 10 of 35 patients. The median time from BMT to nodule detection was 7.8 years. Cytology (n=5) and surgery (n=4) showed no evidence of thyroid cancer. Four of the 14 patients who received cytoreduction without TBI but with busulphan and cyclophosphamide developed UH (n=2) or CH (n=2). We concluded that children who undergo BMT for ALL are at a high risk of subsequent thyroid dysfunction.

Adolescent↗
PubMed2005

Granulocyte colony-stimulating factor for poor graft function after allogeneic stem cell transplantation: 3 days of G-CSF identifies long-term responders.

Poor graft function (PGF) is a frequent cause of morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To study the value of granulocyte colony-stimulating factor (G-CSF) in PGF, we retrospectively analyzed 81 episodes of PGF in 66 patients transplanted from 01/94 to 01/99 from an HLA-identical sibling (n = 45) or an unrelated (n = 21) donor. Median age was 29 years, 55 patients had malignancies. A total of 11 patients received a CD34+ selected graft. Viral infections (25%), myelotoxic drug (33%), fungal/bacterial infections (14%), and GVHD (31%) were present before PGF diagnosis. Median time from allo-HSCT to PGF was 75 (25-474) days. All patients were treated with G-CSF. In 77/81 episodes, there was a response that was sustained in 57. A total of 27 patients presented an increase of white cell count (WBC) >0.1 x 10(9)/l after 3 days of G-CSF. The 5-year survival was 37% and was significantly better in patients with increased WBC > 0.1 x 10(9)/l after 3 days of G-CSF (65 vs 18%, P < 0.0001). In multivariate analysis, increased WBC > 0.1 x 10(9)/l after 3 days of G-CSF (P = 0.002) was associated with better survival, while BuCy-based conditioning (P = 0.02) and GVHD (P = 0.005) were associated with higher risk of death. In conclusion, hematological response after 3 days with G-CSF predicted a better survival for patients with PGF after allo-SCT.

Adolescent↗
PubMed2005

Treatment of chronic hepatitis C virus in allogeneic bone marrow transplant recipients.

We recently reported an increased incidence of cirrhosis in hepatitis C virus (HCV)-infected stem cell transplant (SCT) recipients. Here, we describe our experience in the treatment of these patients, which has been, to date, poorly reported in the literature. Among 99 HCV-infected HCT recipients, 36 had HCV-related liver lesions on biopsy requiring therapy. Owing to HCV treatment contraindications, only 61% of patients (22/36) could be treated. In all, 12 patients received more than one course of anti-HCV treatment if they had HCV RNA still detectable after the first course of treatment and no treatment contraindications. Combined therapy (pegylated interferon (IFN): n=9, or standard IFN: n=9, in combination with ribavirin) led to sustained virological response in 4/18 (20%) patients as compared to 2/20 (10%) in patients who received IFN alone. Hematological toxicity was more frequent with combined therapy. While anemia responded to erythropoietin and/or dose modification, thrombocytopenia usually led to treatment interruption (n=3). This study thus highlights the efficacy of combined therapy and emphasizes the fact that the undue safety concerns are not a problem when treating this particular population.

Adolescent↗
PubMed2005

A 10-year median follow-up study after allogeneic stem cell transplantation for chronic myeloid leukemia in chronic phase from HLA-identical sibling donors.

We report long-term outcome in 102 patients with cCML transplanted from an HLA-identical sibling donor from 1982 to 1998. The conditioning regimen was based on cyclophosphamide associated with either total body irradiation (TBI) (37 patients) or with busulfan (63 patients). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporin and methotrexate in the majority of the patients. Fifteen year overall survival was estimated at 53% (95% confidence interval (CI), 44-65) with a plateau after 2.5 years. Long-term survival was adversely affected by: longer time from chronic myeloid leukemia (CML) diagnosis to transplantation, older age at time of transplantation and GvHD (acute grade III-IV or chronic extensive). The main cause of death was infection, related to GvHD in 69% of patients. Splenectomy also significantly increased the risk of bacterial infection. 15-year relapse was estimated at 8% (95% CI, 0.1-14). Late malignancies occurred in seven patients, four of whom had an invasive cancer. Other frequent late complications included cataracts, psychological depression, osteonecrosis and hypothyroidism. These complications were more frequent following splenectomy, TBI and in patients with chronic extensive GvHD. We conclude that allogeneic transplantation with a related donor can cure more than half of CML patients in chronic phase, although physicians should be alert to long-term complications.

Follow-Up Studies↗
PubMed2003

Allogeneic bone marrow transplantation for acute myeloblastic leukaemia in remission: risk factors for long-term morbidity and mortality.

In this single-centre retrospective study, we analysed risk factors for nonrelapse long-term morbidity and mortality in patients with acute myeloblastic leukaemia (AML) who had undergone allogeneic transplantation. A total of 112 patients with de novo AML in first complete remission (CR1), n=90 or second complete remission (CR2, n=22) who received un-manipulated bone marrow grafts from human leukocyte antigen identical siblings between January 1985 and August 2000 were included. Of these, 97 patients alive and disease-free for at least 100 days after transplant were selected for the purpose of this long-term analysis. The use of an intensified conditioning regimen, Gram-negative bacteriaemia before transplantation, year of transplantation and number of pretransplant chemotherapy courses for patients in CR1 significantly affected the 7-year event-free survival which was 57%. 7-year transplant-related mortality TRM was 22%. Significant predictors for TRM were: bacterial infections before transplantation, major ABO blood group incompatibility, late severe bacterial infections, and chronic (graft-versus-host disease) GvHD. Predictive factors for late severe bacterial infections were infections before transplant, total body irradiation and GvHD. Incidence and risk factors for other late events including, chronic GvHD, late infections, osteonecrosis, cataract, endocrine- cardiac- and lung-complications, cancer and performance status at last follow-up were also studied. The analysis strongly suggests that the combination of pretransplant factors such as chemotherapy and conditioning, and posttransplant factors such as chronic GvHD had a major impact on late nonrelapse morbidity and mortality.

Adolescent↗
PubMed2002

Topical use of cidofovir induced acute renal failure.

BACKGROUND: Cidofovir has antiviral activity against a wide spectrum of DNA viruses. Several small studies have focused on the efficacy of topical cidofovir in various viral-induced diseases. We report a systemic complication of such therapy. CASE REPORT: A bone marrow transplant recipient with chronic renal failure developed genital condylomas resistant to standard therapy. After topical cidofovir application (1% once daily for 5 days, then 4% for 12 days), the lesions improved while local erosions appeared. Acute renal failure with features of tubular acidosis occurred at day 19. Spontaneous recovery was observed after cidofovir withdrawal. CONCLUSION: We describe for the first time acute renal failure after topical cidofovir in an immunosuppressed patient with prior renal insufficiency. This method of administration should be avoided on abraded skin and should be carefully monitored.

Acute Kidney Injury↗
PubMed2002

DPB1 disparities contribute to severe GVHD and reduced patient survival after unrelated donor bone marrow transplantation.

In order to evaluate the impact of HLA-DBP1 incompatibilities on the occurrence of acute graft-versus-host disease (GVHD) in unrelated hematopoietic cell transplantation, we studied 57 donor/recipient pairs characterized by their allelic identity for HLA-A, B, C, DRB1 and DQB1 and also for DRB3, 4, 5 loci and aimed to correlate DPB1 mismatches to already described risk factors for GVHD using multivariate Cox regression analysis. DPB1 identity between donor and recipient was observed in 24% and DPB1 compatibility (GVHD vector) in 42%. Two factors were independently associated with severe acute GVHD: two DP incompatibilities (RR = 8.25, 95% confidence interval (CI): 1.67-40.10, P = 0.010) and disease risk (RR = 10.23, 95% CI: 1.12-93.13, P = 0.012). Two DPB1 incompatibilities appeared also to be a factor in poorer survival independent of its effect on acute GVHD (RR = 4.97, 95% Cl: 1.80-13.71, P = 0.002). A correlation between acute GVHD and matching for each individual DPB1 polymorphic region and for residue 69 of the DP beta molecule, which seems to be a key residue in the alloimmune response, was not observed. Our data indicate that the outcome of unrelated hematopoietic cell transplantation in terms of GVHD but also survival, could be improved through HLA-DPB1 matching or at least by avoiding two DPB1 mismatches.

Adolescent↗
PubMed2001

Toxoplasmic pneumonitis leading to fatal acute respiratory distress syndrome after engraftment in three bone marrow transplant recipients.

Toxoplasmosis is a rare but severe complication of bone marrow transplantation. Here, we report three patients in whom toxoplasmic pneumonitis developed, leading to fatal acute respiratory distress syndrome (ARDS). All patients had positive pretransplantation tests for Toxoplasma gondii and were therefore at risk to develop toxoplasmosis reactivation. They all recovered from aplasia, but soon after they died from brutal and severe ARDS. The possible role of an immunopathologic response to T gondii in the lungs in triggering ARDS is discussed.Early screening of parasitemia using highly sensitive polymerase chain reaction methods in seropositive patients with unexplained fever may be needed.

Acute Disease↗
PubMed2001

Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: long-term follow-up of 4 randomized studies.

In the early 1990s, 4 randomized studies compared conditioning regimens before transplantation for leukemia with either cyclophosphamide (CY) and total-body irradiation (TBI), or busulfan (Bu) and CY. This study analyzed the long-term outcomes for 316 patients with chronic myeloid leukemia (CML) and 172 patients with acute myeloid leukemia (AML) who participated in these 4 trials, now with a mean follow-up of more than 7 years. Among patients with CML, no statistically significant difference in survival or disease-free survival emerged from testing the 2 regimens. The projected 10-year survival estimates were 65% and 63% with Bu-CY versus CY-TBI, respectively. Among patients with AML, the projected 10-year survival estimates were 51% and 63% (95% CI, 52%-74%) with Bu-CY versus CY-TBI, respectively. At last follow-up, most surviving patients had unimpaired health and had returned to work, regardless of the conditioning regimen. Late complications were analyzed after adjustment for patient age and for acute and chronic graft-versus-host disease (GVHD). CML patients who received CY-TBI had an increased risk of cataract formation, and patients treated with Bu-CY had an increased risk of irreversible alopecia. Chronic GVHD was the primary risk factor for late pulmonary disease and avascular osteonecrosis. Thus, Bu-CY and CY-TBI provided similar probabilities of cure for patients with CML. In patients with AML, a nonsignificant 10% lower survival rate was observed after Bu-CY. Late complications occurred equally after both conditioning regimens (except for increased risk of cataract after CY-TBI and of alopecia with Bu-CY).

Adolescent↗
PubMed2001

Human papillomavirus infection and anogenital condyloma in bone marrow transplant recipients.

BACKGROUND: Secondary malignant diseases are late complications after allogeneic bone marrow transplantation (BMT). Anogenital lesions associated with human papillomavirus (HPV) infection have been described in renal transplant recipients but not after BMT. HPV types 16 and 18 are strongly linked to the malignant transformation. METHODS: In a series of 238 patients with allogeneic BMT, three had anogenital lesions. We looked for HPV in DNA extracted from embedded tissue to study HPV genotypes, p53 expression, and ploidy. RESULTS: In two patients, HPV sequences were detected. One of them, with giant condyloma, had HPV type 18 and two aneuploid clones, but p53 expression was not found. CONCLUSION: As in solid organ transplant recipients, anogenital condyloma may develop after BMT. Because the oncoprotein of HPV is able to bind and to degrade p53, it may lead to genetic instability, and subsequently to malignant transformation.

Adult↗
PubMed2001

Influence of bone marrow graft lymphocyte subsets on outcome after HLA-identical sibling transplants.

OBJECTIVE: The aim of this study was to analyze bone marrow lymphocyte subsets and CD34 cell dose and their influence on the outcomes of bone marrow transplantation. MATERIALS AND METHODS: Forty-eight patients (median age 30 years, range 5-54) receiving HLA-identical sibling bone marrow transplantation for hematologic malignancies were analyzed. RESULTS: Median number (range) of nucleated cells and CD34+ cells infused were 2.4 (0.4-6.0) x 10(8)/kg and 3.5 (0.5-13.0) x 10(6)/kg, respectively. Probability of neutrophil recovery was 97%. In a multivariate analysis, time to neutrophil recovery was shortened when a higher number of CD3/CD8 cells was infused (> or =1.0 x 10(7)/kg) (hazard ratio [HR] = 2.13, p = 0.018); when the patient was female or had negative cytomegalovirus serology (HR = 2.03, p = 0.03; HR = 0.41, p = 0.009; respectively). The incidence of grade II to IV acute graft-vs-host disease (GVHD) was 47%. Infusion of >1 x 10(7) CD4 infused/kg increased the risk of acute GVHD (HR = 2.86, p = 0.03). Nineteen of 40 patients at risk experienced chronic GVHD, the risk of which was increased by diagnosis of chronic leukemia (p = 0.03), <2.0 x 10(8) nucleated cells infused/kg (p = 0.05), and a low number of all lymphocyte subsets, except CD19. Estimated 3-year survival rate was 54%. Risk of death was increased in patients receiving <3.5 x 10(6)CD34 infused/kg (HR = 0.37, p = 0.02). Only six patients relapsed. CONCLUSIONS: A high cell dose of CD3/CD8 is associated with faster neutrophil recovery, whereas a high cell dose of CD4+ cells increases the incidence of acute GVHD. A high number of nucleated cells and CD34+ cells infused was associated with decreased risk of chronic GVHD and improved survival, respectively.

Acute Disease↗
PubMed2001

Influence of CD34(+) marrow cell dose on outcome of HLA-identical sibling allogeneic bone marrow transplants in patients with chronic myeloid leukaemia.

In order to study the influence of bone marrow CD34(+) cell dose on the outcome of allogeneic bone marrow transplantation (BMT), we analysed the results of BMT from HLA-identical siblings donors in 50 patients with chronic myeloid leukaemia (CML). The median numbers of nucleated cells (NC) and CD34(+) cells infused were 2.18 x 10(8)/kg (0.05-4.14 x 10(8)/kg) and 3.12 x 10(6)/kg (0.35-8.52 x 10(6)/kg), respectively. All patients engrafted. In univariate analysis, there was no correlation between the number of CD34(+) cells infused and the time to neutrophil recovery (P = 0.17). The Kaplan-Meier estimate of grade II-IV acute graft-versus-host disease (GVHD) at day 100 was 53 +/- 14% and 2-year survival was 46 +/- 15%. A number of CD34(+) cells infused greater than the median was the main factor increasing survival (P = 0.0006) and decreasing 100 day transplant-related mortality (P = 0.009). Patient-, disease- and transplant-related characteristics were not statistically different among patients receiving more or less than the median number of CD34(+) cells. The rate of infectious deaths was significantly higher in patients receiving less than 3.12 x 10(6) CD34/kg (48% vs 16%, P = 0.01). In a multivariable analysis, two factors associated with increased risk of death were advanced disease status at transplant (HR: 2.5 (95% CI: 1.09-5.75), P = 0.03) and a lower number of marrow CD34(+) cells infused/kg (HR: 4.55 (95% CI: 1.87-10.90), P = 0.0008).

Adolescent↗
PubMed2001

Health and functional status of adult recipients 1 year after allogeneic haematopoietic stem cell transplantation.

Increasing numbers of patients are surviving after allogeneic haematopoietic stem cell transplantation (SCT). Among these patients, a number of late complications have been described but few data on the risk factors of these long-term effects of SCT are available. We report the analysis on 105 adult patients, surviving free of haematological disease at a median time of 15 months after SCT. At the time of screening, 52% had returned to work, general health status was normal in 67% and 47% were sexually active. Female patient gender odds ratio (OR) 2.9 (P = 0.01) and age > 25 years (OR = 3.2, P = 0.02) were associated with non-return to work. Decreased general status was associated with chronic graft-versus-host disease (GvHD) (OR = 3.2, P = 0.009) and irradiation (OR = 3.6, P = 0.004). Sexual inactivity was associated with younger age (OR = 7.0, P = 0.0002) and chronic GvHD (OR = 3.3, P = 0.006). Risk factors for altered pulmonary function tests included previous smoking habits, irradiation and chronic GvHD. Obstructive lung disease was associated with a previous history of asthma. Sicca syndrome and conjunctivitis were increased in patients with previous acute GvHD and cataracts were less frequent in patients with aplastic anaemia. Persistent impaired hair re-growth was less frequent in patients who received irradiation (OR = 0.18, P = 0.002) but increased in patients with previous acute GvHD (OR = 5.3, P = 0.007). Microalbuminuria was more frequent in irradiated patients (OR = 9.4, P = 0.05). Raised cholesterol was associated with age (OR = 20.8, P < 0.001), previous acute GvHD (OR = 4.7, P = 0.03), steroid use (OR = 6.3, P = 0.001) and familial hypercholesterolaemia (OR = 4.4, P = 0.04). Decreased bone density was associated with chronic GvHD (OR = 3.9, P = 0.001). Thus, using routine tests in adult patients we were able to detect significant numbers of-non-symptomatic complications enabling early treatment.

Acute Disease↗
PubMed2001

Prolonged immune deficiency following allogeneic stem cell transplantation: risk factors and complications in adult patients.

To evaluate the long-term immune reconstitution after allogeneic haematopoietic stem cell transplantation (SCT), we prospectively screened standard immune parameters in a series of 105 patients, at a median time of 15 months after SCT. Analysing lymphoid phenotypes, in vitro immune functions and immunoglobulin levels, we found that, more than 1 year post SCT, cellular and humoral immunity was still altered in a significant number of patients. CD4+ T cells were < 200/microl in one third of patients, and the CD4/CD8 ratio was still reversed in 78% of patients. Almost all patients showed positive T-cell responses against mitogens, but antigen-specific proliferation assays identified 20% to 80% of non-responders. B-cell counts were reconstituted in 61% of the patients, but levels of total immunoglobulins were still low in 59%. In multivariate analyses, human leucocyte antigen (HLA) disparity between donor and recipient and chronic graft-versus-host disease were the leading causes affecting immune reconstitution. Interestingly, cytomegalovirus (CMV) infections were strongly associated with normal CD8+ T-cell counts. Studying the impact of impaired immune reconstitution on the rate of infections occurring in the 6 years following screening, we identified three parameters (low B-cell count, inverted CD4/CD8 ratio, and negative response to tetanus toxin) as significant risk factors for developing such late infections.

Adolescent↗
PubMed2000

Resistant herpes simplex virus type 1 infection: an emerging concern after allogeneic stem cell transplantation.

Fourteen cases of severe acyclovir-resistant herpes simplex virus type 1 (HSV-1) infection, 7 of which showed resistance to foscarnet, were diagnosed among 196 allogeneic stem cell transplant recipients within a 29-month period. Recipients of unrelated stem cell transplants were at higher risk. All patients received foscarnet; 8 subsequently received cidofovir. Strains were initially foscarnet-resistant in 3 patients and secondarily so in 4 patients. In vitro resistance to acyclovir or foscarnet was associated with clinical failure of these drugs; however, in vitro susceptibility to foscarnet was associated with complete response in only 5 of 7 patients. No strain from any of the 7 patients was resistant in vitro to cidofovir; however, only 3 of 7 patients achieved complete response. Therefore, acyclovir- and/or foscarnet-resistant HSV-1 infections after allogeneic stem cell transplantation have become a concern; current strategies need to be reassessed and new strategies must be evaluated in this setting.

Acyclovir↗