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The incidence and potential clinical consequences of bacterial contamination of autologous and allogeneic BM products remains open to question. We report our experience of bacterial contamination of BM grafts and adverse events that occurred after transplantation.From January 2003 to February 2006, 257 BM harvests were processed and infused at our institution. Analysis of microbial contamination incidence before and after processing, sensitivity spectra of isolated bacteria and adverse events after graft infusion were analyzed.Nineteen of 257 BM (7.4%) were contaminated. Coagulase-negative Staphylococcus (n=9) and Propionibacterium acnes (n=6) were the most frequently isolated microorganisms. Two of nine coagulase-negative staphylococci were found to be resistant to erythromycin and two of six P. acnes to fosfomycin and gentamycin. The frequency and severity of immediate adverse events reported in patients receiving a contaminated graft were similar to those observed in patients receiving a non-contaminated product. No major adverse sequelae occurred after infusion of contaminated grafts. Finally, none of the patients transplanted with a contaminated graft developed bacteriemia that could have been related to the isolated microorganism.Microbial contamination of BM progenitor cell grafts does not induce severe clinical complications or infectious diseases after infusion. The vast majority of isolated pathogens were skin contaminants.

BACKGROUND: Red cell (RBC) depletion is needed to bypass ABO mismatch in allogeneic bone marrow transplantation (BMT). Technical and clinical data obtained after bone marrow (BM) processing with a continuous-flow cell separator (Cobe Spectra, Gambro BCT) are reported. STUDY DESIGN AND METHODS: RBC depletion and recovery of nucleated cells, CD3+ cells, CD34+ cells, and colony-forming unit–granulocyte-macrophage were calculated. Bacteriologic contaminations, side effects of graft infusion, and hematopoietic recovery were analyzed. RESULTS: A total of 114 BM samples were processed. The mean volume collected was 1099 mL (range, 390-2450 mL). Initial and residual mean RBCs volumes were 309.9 and 4.0 mL corresponding to a depletion of 98.6 ± 0.78 percent. Before processing, the mean numbers of nucleated cells, granulocytes, CD3+ cells, CD34+ cells, and CFU-GM were 20.28 × 109, 12.79 × 109, 1.96 × 109, 356.7 × 106, and 195.6 × 105, respectively. The mean corresponding recoveries after processing were 33.66, 48.98, 82.02, 82.2, and 93.9 percent. Limited side effects were observed in 14 patients without correlation with residual RBCs volume. All but two patients engrafted. CONCLUSION: BM processing with the Cobe Spectra cell separator provides high rates of RBC depletion without significant side effects after BMT.

Objectives Platelet products have been proposed as adjuvant therapy for wound healing. We undertook this study to determine the healing effect of topically applied frozen autologous platelets (FAP) on chronic venous ulcers, compared with effect of placebo, and whether use of topical FAP modifies local expression of vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), interleukin 8 (IL-8), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in wound fluid. Methods This randomized, placebo-controlled, double-blind trial was carried out in institutional practice, with ambulatory patients with proved chronic venous leg ulcers. In all patients, whole venous blood was drawn for preparation of FAP. FAP or normal saline solution was applied three times per week for up to 12 weeks, together with hydrocolloids and standardized compression bandages. Leg ulcer surface was assessed with numerical pictures. IL-8, VEGF, KGF, and TIMP-1 levels were determined (enzyme-linked immunosorbent assay) in wound fluid after each 4 weeks of treatment. Results Fifteen patients were randomized into two groups with comparable leg ulcer characteristics. Mean percent reduction in ulcer area was 26.2% in the FAP group versus 15.2% in the placebo group ( P = .94). One ulcer in each group was completely healed at study end. Levels of TIMP-1 increased significantly during FAP treatment. IL-8 concentration was significantly lower in wound fluid of healing ulcers than in the fluid of nonhealing ulcers, in both FAP and placebo groups. Growth factor levels were not modified with FAP treatment. Conclusion Topical autologous platelets have no significant adjuvant effect on healing of chronic venous leg ulcers and increased wound fluid TIMP-1 concentration. Ulcer healing is associated with a decrease in wound fluid IL-8.

Allogeneic transplantation is the only curative treatment for Fanconi anaemia (FA) patients who develop myeloid malignancies. Dose-intensive preparative regimens, to decrease disease recurrence, lead to unacceptable transplant-related toxicity in FA. We report the outcome of three FA patients with such malignancies who underwent transplantation with reduced-intensity preparative regimens. This approach was well tolerated, even as second transplantations, and resulted in complete leukaemic remissions. However, the graft-versus-leukaemia effect was associated with fatal graft-versus-host disease. Even after transplantation, myeloid malignancies remain associated with a poor outcome in FA, and this argues in favour of early intervention when suitable donors are available.

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).

Summary: Glanzmann’s thrombasthenia is an autosomal recessive disorder characterized by a lack of platelet aggregation due to the absence of platelet glycoprotein IIb and IIIa. Usually, the disease leads to mild hemorrhage but sometimes bleeding is severe enough to be life-threatening. We report the case of a 16-year-old girl, presenting with very severe type 1 Glanzmann’s thrombasthenia, successfully treated with an HLA-identical sibling bone marrow transplant (BMT). We also update the clinical and laboratory data of her brother, who had received a BMT 16 years ago for the same disease. In the light of these two cases and two others published in the literature, we discuss the indications for BMT from HLAidentical sibling donors in Glanzmann’s thrombasthenia. Alloimmunization against the missing platelet GPIIb/IIIa complex and severity of bleeding episodes may constitute sufficient criteria for allogeneic BMT after careful assessment of the risk-benefit of such a procedure, although this remains exceptional in this disease. Bone Marrow Transplantation (2000) 25, 327‐ 330.

Umbilical cord blood collected and cryopreserved at birth contains enough hematopoietic progenitor stem cells for engraftment. HLA identical sibling cord blood transplantation has been performed for the first time in a child with Fanconi's anemia. This child is alive 3 years later with a complete donor type bone marrow. Since this first attempt, several other patients with other diseases have been transplanted successfully. Cord blood banking is a safe and easy procedure. Due to the high proliferative capacity of neonatal hematopoietic progenitors and to the relative immunological functional immaturity of neonatal lymphocytes, cord blood cells could be used for matched unrelated or partially mismatched transplants.

Major ABO incompatibility between donor and recipient is not considered a barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT), even if it can be associated with several immunohematologic complications. Nevertheless, conflicting data still exist as to its influence on graft-versus-host disease (GVHD) incidence, relapse rate, and survival. To further investigate the relevance of ABO major mismatch on transplantation outcome, we retrospectively analyzed results from 414 patients with major or major/minor ABO-mismatched bone marrow (BM), peripheral blood (PB), and cord blood (CB) allogeneic HSCT. Transplantation outcome was assessed by comparison with results from a 395-patient ABO-compatible population with similar characteristics. Median time to red cell transfusion independence was significantly longer in ABO-incompatible BM recipients (median time, 63 days vs 41 days; P =.001), with faster disappearance of antidonor IgM hemagglutinins in unrelated recipients (median time, 36 days vs 44 days; P = .03) and in patients with gradeor =II acute GVHD (aGVHD) (median time, 35 days vs 59 days ; P = .001). In PB stem cell (PBSC) and CB transplantation, erythroid reconstitution was not significantly delayed, regardless of donor type or presence of aGVHD. A slight correlation between ABO incompatibility and GVHD incidence was found in PBSC recipients when considering gradeor =II aGVHD incidence (63% in ABO-matched HSCT vs 83% in ABO-mismatched HSCT; P = .055), but this was not confirmed in multivariate analysis. In patients with acute leukemia, multivariate analysis revealed an association between major ABO mismatch and decreased relapse rate with borderline statistical significance (hazard ratio, 0.65; P = .04). Major ABO incompatibility mainly, if not exclusively, affects red blood cell engraftment after BM transplantation. Somewhat surprisingly, the graft-versus-plasma cell effect seems to be confined to this stem cell source.

Summary Patients with bone marrow failure syndromes (BMFS) who reject a first allogeneic transplant or fail immunosuppressive therapy (IST) have an especially grim prognosis. We report 14 patients (eight adults, six children) transplanted with double cord blood transplantation (dUCBT) for BMFS. Neutrophil recovery was observed in eight patients, with full donor chimerism of one unit, and acute GVHD in 10. With a median follow-up of 23 months, the estimated 2 years overall survival was 80 ± 17% and 33 ± 16% for patients with acquired and inherited BMFS, respectively. Transplantation of two partially HLA-matched UCB thus enables salvage treatment of high-risk patients with BMFS.

Graft failure (GF) can be a fatal complication following haematopoietic stem cell transplantation (HSCT). We report four patients who developed early GF after unrelated HSCT and who subsequently received a double unrelated cord blood transplant (dUCBT) after reduced-intensity conditioning, at a median 15 d after the decision to perform a second transplant. Neutrophil recovery was observed in all four patients between day +15 and +31 with full donor chimaerism of one unit. Acute GVHD grades II-IV was observed in three patients. Three are alive, between 12 and 25 months after dUCBT. In conclusion, dUCBT is a promising procedure to treat early GF.

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.

From January 1978 to December 2001, 133 patients with severe aplastic anemia (SAA) underwent non-T cell-depleted allogeneic bone marrow transplantation from an HLA-identical sibling donor, at the Hospital Saint Louis using either the combination of cyclophosphamide (Cy) and thoracoabdominal irradiation (TAI; n = 100) or Cy and antithymocyte globulin (ATG; n = 33), as a conditioning regimen. With 13.6 years of follow-up, the 10-year survival estimate was 64%. Four factors were associated with lower survival: older age, use of Cy-TAI, any form of treatment prior to transplantation (either androgens or immunosuppressive therapy, [IST]), and grade II to IV acute graft-versus-host disease (GvHD). TAI was the sole factor associated with the occurrence of acute GvHD. The risk of cancers (15-year cumulative incidence, 10.9%) was associated with older age and with the use of cyclosporine as IST before transplantation. Cumulative incidences and risk factors of nonmalignant late effect including avascular osteonecrosis and late bacterial, viral, and fungal infection were also analyzed. Improved results using Cy-ATG as conditioning can lead to more than 90% chance of cure in patients with SAA. Even if, in our experience, the role of Cy-ATG versus that of Cy-TAI remained inextricably related to the year of transplantation, the major detrimental role of the GvHD disease in the long-term outcome and its relation to TAI supports avoidance of irradiation in the conditioning regimen. Furthermore, avoidance of any IST before transplantation in patients with a sibling donor is a prerequisite for attaining such excellent results.

To assess whether Fanconi anemia (FA) patients might be at risk for acute graft-versus-host disease (AGvHD) despite using low-intensity conditionings, we retrospectively analyzed the incidence of AGvHD and its impact on outcome in 37 FA patients and 73 patients with acquired aplastic anemia (AAA) that received transplants at Saint Louis Hospital from HLA-genotypic identical siblings with similar conditionings (thoraco-abdominal irradiation plus cyclophosphamide 20 [FA] or 150 mg/kg [AAA]). Despite being younger, FA patients had an increased risk of grades II to IV AGvHD (relative risk [RR], 2.00; P = .021), especially in younger patients (RR, 7.93; P = .014). The risks of requiring systemic corticosteroids to treat AGvHD and experiencing cortico-resistant AGvHD were significantly increased in FA patients. Although non-FA and FA patients had similar 10-year outcomes, acute and chronic GvHD had a biphasic effect on FA patient outcome with an additional cluster of lethal events starting by 5 years after transplantation. This late survival fall, restricted to FA patients, was closely related to head and neck carcinomas (15-year incidence: 53%). FA patients represent a group at risk regarding AGvHD when using irradiation-based conditionings. The impact of AGvHD on survival may not be limited to the early posttransplantation period and may be a major risk factor for head and neck carcinomas and late mortality in FA patients.

To study the prevalence and clinical features of hepatitis G virus (HGV)/GB virus C (GBV-C) infection in bone marrow transplantation (BMT), we examined frozen serum samples from 95 bone marrow allograft patients for HGV/GBV-C RNA by RT-PCR. Twenty-eight out of 95 (29.5%) were positive and 14 of the HGV+ patients were already positive before transplantation. The mean numbers of blood donors to whom the HGV and HGV+ populations were exposed before BMT were not significantly different (Kruskal-Wallis test, P = 0.08, NS) but did reveal that the HGV+ population had been transfused more often. Moreover, all but one of the patients who were HGV+ before graft, had had hematological diseases which needed heavy transfusion protocols suggesting, a role of blood products in HGV transmission. Fifty out of the 95 patients received Gammagard intravenous immunoglobulin (i.v.IG) batches suspected of having transmitted HCV. However, no significant difference appeared between these recipients and those receiving other i.v.IG. Despite their immunodeficiency, no clinical or biological evidence of liver disease potentially linked to HGV infection has as yet been observed. The clinical outcome, in terms of acute GVHD, chronic GVHD or veno-occlusive disease was similar in HGV+ and HGV- recipients suggesting the absence of adverse effects of HGV infection on the early outcome of allogenic BMT. Long-term evolution remains to be prospectively studied.

Human umbilical cord blood was evaluated as an alternative to bone marrow as a source of stem cells for hematopoietic transplantation. In order to define an optimal collection procedure, we have studied the parameters that influence the collection, handling and storage of cord blood. We have attempted to correlate the quality of the samples with obstetrical and neonatal parameters. Using culture techniques we have studied the long term viability of the cells. Cell separation was also investigated. Our results suggest that most of the sample collected could be suitable for transplantation, in term of progenitors. However the observed variability between samples suggest that an efficient control of the quality of the samples is important.

Umbilical cord blood collected and cryopreserved at birth contains enough hematopoietic progenitor stem cells for engraftment. HLA identical sibling cord blood transplant has been performed for the first time, in a child with Fanconi anemia. Three years latter, this child is alive with a complete donor type bone marrow. Since this first attempt, several other patients with other diseases have been transplanted successfully. Cord blood banking is a safe and easy procedure. Due to the high proliferative capacity of neonatal hematopoietic progenitors and to the relative immunological functional immaturity of neonatal lymphocytes cord blood cells could be used for matched unrelated or partially mismatched transplants.

Since 1980, 107 consecutive patients (pts) underwent bone marrow transplantation (BMT) for nonconstitutional severe aplastic anemia (SAA) at our institution. All received conditioning with Cytoxan (150 mg/kg) and thoraco-abdominal irradiation (6 Gy) from an HLA-identical sibling donor. Mean age was 19 years (5 to 46 years). Forty-nine pts had less than 0.2 x 10(9)/L PMN and 53 failed to respond to previous immunosuppressive therapy before BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate (22 pts), cyclosporine (52 pts), or both (33 pts). With a median follow-up of 45 months (12 to 120 months), overall actuarial survival was 68% (confidence interval 95%:9.7). Of 16 factors tested, five were shown to adversely influence survival by multivariate analysis: grade greater than or equal to 2 acute GVHD (relative risk [RR]: 5.5), prior immunosuppressive therapy (RR: 3.5), female as donor (RR: 2.4), nonidiopathic SAA (RR: 2), and more than 0.2 x 10(9)/L PMN AA (RR: 2). Because acute GVHD was the most potent factor for survival, we analysed risk factors for acute GVHD. By multivariate analysis, 2 of 14 factors tested were independent: male as recipient (RR: 3) and previous alloimmunization of the donor (RR: 4.3). On long-term follow-up, chronic GVHD was observed in 49 pts of 89 surviving more than 100 days (55%). Multivariate analysis showed that infection before transplant (RR: 1.3) and previous history of acute GVHD (RR: 1.8) were associated with an increased risk of chronic GVHD.

We studied the conditions of collection and isolation of hematopoietic cells from cord blood in order to optimise the sampling. A statistically significant correlation was found between the total stem cell content of the samples and the time of delivery suggesting that the quantity of hematopoietic stem cells available is higher when cord blood collection is performed earlier during pregnancy. Attempt to isolate the white cells resulted in a dramatic loss of stem cells. Factors affecting cell recovery and purification must be investigated in order to optimize cord blood cell banking.

It has been shown that human umbilical cord blood contains stem/progenitor cells comparable in number to that of adult bone marrow. We report here the first successful cases of transplantation of umbilical cord blood cells. The patients were suffering from Fanconi's anemia, complicated by severe aplastic anemia. During pregnancy, it was shown that the mother was carrying a sibling unaffected by the disease and with HLA identical to the patient. Cord blood was collected and frozen in liquid nitrogen at birth. After conditioning with low-dose cyclophosphamide (20 mg/kg) and thoraco-abdominal irradiation (5 grays), the patients received a cord blood transplant of thawed cells. Three patients have been transplanted without any immediate side-effect. One has not enough follow-up, but two patients are alive and well with complete donor hematologic reconstitution and no chronic graft versus host disease. Potential developments of this technique are an extension of applicability with regard to other diseases that might be transplanted and whether such transplants can be performed in adults. The relative immaturity of the lymphoid system at birth may be advantageous in decreasing the graft versus host reaction if these cells are used in a mismatched transplantation. Cord blood cell banks may be useful for transplants in patients lacking an HLA-identical donor.

Collection of placental blood in a sterile and closed system is a simple, safe and efficient procedure. One hundred and fifty eight units of fetal blood were collected by applying the same requirements of quality and safety as those defined for blood products in blood banks. No adverse effects were seen in mothers or their newborns.

This paper reviews the experience in the collection of 67 cord blood for use in sibling transplants. Details are given on the mean volumes collected, the numbers of nucleated cells, the CFU-GM and BFU-E obtained, and the incidence of collection failure.

Between August 1979 and April 1986, we treated 70 patients with chronic myeloid leukemia by supralethal chemoradiotherapy followed by bone marrow transplantation (BMT) from HLA identical sibling donors (65 patients) or from identical twins (5 patients). All patients were splenectomized before BMT. To prevent graft versus host disease Cyclosporin alone or associated with Methotrexate was given; in addition 13 patients received a T cell depleted marrow. All patients showed engraftment. Of the 5 patients treated by syngenic BMT, 2 patients relapsed but all are alive in remission, 2 of them after a successful second BMT. Of the 36 patients treated by allogeneic BMT in the chronic phase, 20 are alive in unmaintained remission after a median follow-up of 24 months (range 6 to 58). No patients have relapsed. The actuarial survival at 2 years was 60%. Of the 29 patients with more advanced disease, 19 have survived with the actuarial survival at 2 years 50%. We conclude that the probability of cure after BMT is very high, especially if BMT is performed while the patient remains in the chronic phase. Only 3 patients grafted in accelerated or blast phase died with relapse. The main cause of death was interstitial pneumonitis (15 patients) and 10 patients died from other transplant-related complications.