A prospective study of a long-term follow-up of an observation program for neuroblastoma detected by mass screening.

BACKGROUND: A nationwide mass screening for neuroblastoma (NBL) in 6-month-old infants (MS6M) was performed in Japan from 1985 to 2003. Favorable biological features were identified for most of the detected tumors; consequently, we began an observation program for selected screened patients in 1993. Here, we report the clinicopathological findings and present status of patients enrolled in our observation program, with the goal of evaluating its usefulness. PROCEDURE: Between 1993 and 2003, 53 of 101 patients with NBL detected by MS6M were enrolled. The patients were divided into four groups according to changes in urinary VMA and HVA levels and tumor size. RESULTS: Urinary VMA and HVA levels decreased in 39 of 53 patients. In 17 of these 39 patients, the tumor became undetectable (Group A); in 22 patients the tumor was detectable (Group B). In seven patients, tumor marker levels varied, and tumor volume gradually increased (Group C). In six patients, tumor marker levels and tumor volume increased in the short term (Group D). One patient had multiple tumors (1M according to International Neuroblastoma Staging System). All tumors in Groups C and D, four tumors in Group B, and one tumor in the 1M patient were removed. No unfavorable biologic factors were noted in any excised tumor. CONCLUSIONS: The observation program of the present study, one of the largest series for MS6M, confirmed that over 70% of patients who fulfilled the criteria could be observed without surgery.

Cord blood transplantation from HLA-mismatched unrelated donors.

The results for 49 patients with hematologic and non malignancies who were subjected to a cord blood transplantation from HLA-mismatched unrelated donors (UCBT) are presented here. This retrospective study included 22 patients with acute lymphoblastic leukemia, 12 with acute myelogenous leukemia, one each with chronic myelogenous leukemia, refractory anemia with myelodysplastic syndrome, and juvenile myelomonocytic leukemia, three with Wistott-Aldrich syndrome, three with adrenoleukodystrophy, two with Hunter's syndrome, one each with Hurler's syndrome, purine nucleotide phosphorylase deficiency, pure red cell aplasia, and severe aplastic anemia. In malignant diseases, the Kaplan-Meier estimates for three-year overall survival (OAS) and event-free survival (EFS) were 51.9 +/- 17.8, and 51.4 +/- 17.8%, respectively. In patients with non malignant disease, the Kaplan-Meier estimates for three-year OAS and EFS were 64.2 +/- 28.8, and 37.5 +/- 29.4%, respectively. In patients with malignancy, the HLA disparity had no effect on OAS, EFS, incidence of acute graft-versus-host disease, or engraftment. On the other hand, for engraftment, the use of UCBT from HLA-mismatched unrelated donors may require a larger study in patients with non-malignant diseases.

Cord blood transplantation from unrelated donors: a preliminary report from the Japanese Cord Blood Bank Network.

As a source for hematopoietic stem cell transplantation (HSCT), cord blood transplantation from unrelated donors (UCBT) is now considered as an acceptable alternative to patients who need unrelated HSCT. To confirm the findings that mismatched UCBT is feasible, we discussed here the results for 477 patients with hematologic malignancies and non-malignancies who were subjected to UCBT coordinated by the Japanese Cord Blood Bank Network (JCBBN). From February 1997 to October 2001, 411 patients with malignancies and 66 with non-malignancies had UCBT through the cord blood bank in the JCBBN; 311 patients had HLA 0-1 mismatched UCBT; 165, had a 2-4 HLA mismatch. The Kaplan-Meier estimates for 3-year disease-free survival rate (DFS) were 35.2 +/- 2.8% in malignant diseases, and 33.6 +/- 7.2% in patients with non-malignant diseases. The HLA disparity had no effect on DFS, incidence of acute graft-versus-host disease, or engraftment. As reported previously, we also noted the importance of graft cell dose in determining survival in UCBT. Major advantages of UCBT include its rapid availability compared with unrelated donor bone marrow, and tolerance of an HLA mismatch at 2 loci, which will enable extension of the donor pool. This review outlines the latest UCBT progress, with emphasis on practical considerations in HLA-mismatched umbilical cord blood selection.

Quality of long-term cryopreserved umbilical cord blood units for hematopoietic cell transplantation.

The aim of this study was to evaluate the quality of long-term cryopreserved umbilical cord blood (CB) units for hematopoietic cell transplantation (HCT). The recovery of the number of total nucleated cell (TNC), hematopoietic progenitor cells (HPCs; CD34+ cells, colony-forming units-granulocyte/macrophages [CFU-GMs]), and the percentage of viable cells, CD34+ CD38- cells, and CD34+ CXCR4+ cells of CB units cryopreserved for 10 years for HCT were examined. Eighteen CB units cryopreserved for 10 years (as the study group) and for 1 month (as the control group), respectively, were analyzed. The recovery rate of TNC, CD34+ cells and CFU-GMs were 88.72 ± 16.40, 68.39 ± 18.37 and 42.28 ± 38.16% for the study group and 80.17 ± 14.46, 72.67 ± 20.38 and 49.61 ± 36.39% for the control group (p = 0.106, p = 0.513 and p = 0.559, respectively). There were no significant differences in the recovery rate of TNC, CD34+ cells and CFU-GMs between the study group and the control group. The mean basal percentage of viable cells, CD34+ CD38- cells, and CD34+ CXCR4+ cells after thawing were 83.69 ± 9.45, 9.11 ± 4.13 and 81.65 ± 10.82% for the study group. These results indicate that long-term cryopreservation does not negatively affect the quality of CB units for HCT.

Unrelated cord blood transplantation for second hemopoietic stem cell transplantation.

BACKGROUND: The Kanagawa Cord Blood Bank (KCBB) reports the treatment of 12 patients who received umbilical cord blood transplantation (CBT) from unrelated donors as their second hemopoietic stem cell transplantation (HSCT). METHODS: Provided by the KCBB, between February 1997 and September 2000, 12 patients had unrelated CBT as a second HSCT. Six patients were male and six female; nine patients were in malignant, and three were in non-malignant conditions. The median age of the patients was 7.9 years (range, 2.2-28.0), and the median bodyweight was 22.5 kg (12.0-55.0). The HLA-A and -B serological and DR genotypical disparities between the patients and CBT donors were as follows: one patient was a 0-mismatch, six were 1-mismatches, and five were 2-mismatches. RESULTS: The median time between first and second HSCT was 14.0 months (1.0-47.0). The overall survival rate was 25.0%, three years after CBT (Kaplan-Meier estimate). Mortality after CBT as a second HSCT accounted for nine cases, six from infection and three from treatment-related mortality other than infection. CONCLUSION: Cord blood transplantation offers the advantage of rapid availability, absence of donor risk, and possibly less HLA restriction. In these contexts, unrelated CBT should be considered as a source of HSCT for a second transplant.

The Japanese cord blood bank network experience with cord blood transplantation from unrelated donors for haematological malignancies: an evaluation of graft-versus-host disease prophylaxis.

Cryopreserved umbilical cord blood (CB) from unrelated donors can restore haematopoiesis after myeloablative therapy in patients with haematological malignancy. We investigated the clinical outcomes of CB transplantation (CBT) with special emphasis on graft-versus-host disease (GVHD) prophylaxis. Patients with haematological malignancies (n = 216) received intensive chemotherapy or immunosuppressive therapy, followed by transplantation of cryopreserved CB cells from unrelated donors. The clinical outcomes, i.e. haematological reconstitution, the incidence of acute or chronic GVHD, relapse and event-free survival (EFS), were evaluated. The estimated probability of neutrophil recovery was 88.2%. The median follow-up for the survivors was 557 d (range 21-1492 d). The overall and EFS rates were 32.6% and 25.5%, respectively, 3.5 years after transplantation. Multivariate analysis using Cox's proportional hazards model showed that high-risk disease status at CBT and single-drug GVHD prophylaxis were associated with worse 2-year EFS rates [P = 0.0013, relative risk (RR) 1.90, 95% confidence interval (CI) 1.28-2.81 and P = 0.0007, RR 1.91, 95% CI 1.31-2.79 respectively). Age at CBT had no significant influence on EFS. Cryopreserved CB from unrelated donors can restore haematopoiesis in patients with haematological malignancy. Although the incidence is low, the prophylaxis for acute GVHD is an important factor for survival of CBT from unrelated donors. A high rate of suitable donors was found, with a probability of 1 to every 18 CB units, when compared with human leucocyte antigen matching at other haematopoietic stem cell banks.