Successful unrelated cord blood transplantation in an infant with Wiskott-Aldrich syndrome following recurrent cytomegalovirus disease.

We describe successful unrelated cord blood transplantation in a 14-month-old boy with Wiskott-Aldrich syndrome. He had been suffering from recurrent cytomegalovirus (CMV) pneumonia. Ganciclovir was given pretransplantation and posttransplantation, and CMV antigenemia was monitored as a marker of reactivation. The conditioning regimen was cyclophosphamide, busulfan, and antithymocyte globulin. The patient received an HLA 1-locus-mismatched cord blood unit, and the total number of infused nucleated cells was 9.0 x 10(7)/kg. Neutrophil engraftment was achieved on day +20, and a platelet count greater than 50 x 10(9)/L was achieved on day +51. A normal lymphoproliferative response to phytohemagglutinin mitogen was detectable 7 months posttransplantation. Long-term use of ganciclovir prevented CMV reactivation and did not compromise engraftment.

Effect of granulocyte colony-stimulating factor on bone metabolism during peripheral blood stem cell mobilization.

Granulocyte colony-stimulating factor (G-CSF) has been shown to affect the biochemical markers of bone metabolism, including serum bone alkaline phosphatase (BALP), serum osteocalcin, and urine deoxypyridinoline. To determine the association between bone resorption and formation and the G-CSF-induced mobilization of peripheral blood stem cells (PBSC), we examined these markers during mobilization in 19 healthy donors. The average (+/- SEM) serum BALP level before treatment was 81.6 +/- 17.0 IU/dL, and the level increased significantly to 117.7 +/- 15.8 IU/dL on day 5 of G-CSF administration (P < .0001). The urine deoxypyridinoline level before treatment was 12.3 +/- 2.4 nmol/mmol creatinine, and this level also increased significantly to 19.4 +/- 3.0 nmol/mmol creatinine on day 5 of G-CSF administration (P < .0001). In contrast, the average level of serum osteocalcin significantly decreased from 8.07 +/- 2.88 ng/mL to 1.53 +/- 0.18 ng/mL on day 5 (P = .0353). During G-CSF administration, we also studied the serum levels of various cytokines (IL-1beta, osteoclastogenesis inhibitory factor [OCIF], IL-6, tumor necrosis factor alpha, transforming growth factor beta, interferon-gamma, macrophage colony-stimulating factor) related to bone metabolism. Only the kinetics of OCIF were significantly affected. The serum level of OCIF increased immediately after the start of G-CSF administration and remained high during G-CSF administration. These results demonstrate that high-dose G-CSF affects bone metabolism and that OCIF may play a role in bone metabolism. Consistent with the notion that G-CSF affects bone metabolism, a significant correlation was observed between CD34+ cell yield and the increase in urine deoxypyridinoline but not for the changes in serum BALP and osteocalcin levels. This result suggests that bone resorption is either directly or indirectly related to the mobilization of PBSC by G-CSF.

Treatment of unresectable malignant rhabdoid tumor of the orbit with tandem high-dose chemotherapy and gamma-knife radiosurgery.

Malignant rhabdoid tumor (MRT) is a rare and highly aggressive tumor that primarily occurs in very young children. We report here a patient with a primary MRT of the orbit who received tandem high-dose chemotherapy and gamma-knife radiosurgery. Although the tumor was not completely removed, and the initial chemotherapy failed, the patient achieved long-term survival after this modality of treatment. This approach may be one to be further considered in patients with MRT.

Successful high-dose chemotherapy for widespread neuroaxis dissemination of an optico-hypothalamic juvenile pilocytic astrocytoma in an infant: a case report.

We report a 13-month-old boy with diencephalic syndrome (DS) due to an optico-hypothalamic juvenile pilocytic astrocytoma (JPA). Massive neuroaxis dissemination was identified at diagnosis. He received 6 courses of combined conventional-dose chemotherapy consisting of carboplatin (CBDCA), etoposide (VP-16), and cyclophosphamide (CPA) followed by high-dose chemotherapy with CBDCA, CPA, and ranimustine (MCNU) and peripheral blood stem cell transplantation (PBSCT). This treatment produced tumor regression in both intracranial and spinal lesions and remarkable improvement of DS. The rare combination of DS and symptomatic neuroaxis dissemination of JPA at diagnosis suggests that the behavior of some of these tumors is more aggressive and resistant to conventional-dose chemotherapy than is that of JPA without DS manifestation and dissemination.

Analysis of maternal and neonatal factors that influence the nucleated and CD34+ cell yield for cord blood banking.

BACKGROUND: It would be beneficial to be able to predict the cord blood (CB) cell yield from volunteer donors before cell processing. STUDY DESIGN AND METHODS: The maternal and neonatal factors that influence the total nucleated cell (TNC), CD34+ cell, and CFU-GM yields in CB collected for the Chugoku-Shikoku Cord Blood Bank were evaluated. RESULTS: In a univariate analysis, the volume of CB collected was significantly correlated with the TNC, CD34+ cell, and CFU-GM yields (p < 0.001). A longer cord (p < 0.001), larger placenta (p < 0.001), and bigger baby (p < 0.001) were associated with a greater volume of CB. A female baby (p < 0.05) and longer gestational age (p < 0.005) were associated with a higher TNC concentration. A younger maternal age (p < 0.05), larger birth weight (p < 0.001), shorter gestational age (p < 0.001), and shorter time from collection to processing (p < 0.05) were associated with a higher CD34+ cell concentration. A multivariate linear regression analysis was performed to predict the yield and determine first-level selection criteria to start processing when the volume of CB units was on the borderline. However, this formula might not be suitable for actual use. CONCLUSION: Maternal and neonatal factors appeared to affect CB cell yields. These findings might be useful for efficiently collecting more qualified CB units.

Cryopreservation of mobilized blood stem cells at a higher cell concentration without the use of a programmed freezer.

Cryopreservation of peripheral blood stem cells (PBSC) mobilized by chemotherapy combined with or without granulocyte colony-stimulating factor (G-CSF) is an essential part of procedure for anti-cancer strategies. We evaluated whether a higher cell concentration (2 x 10(8)/ml) without the use of a programmed freezer was acceptable for the storage of mobilized PBSC in an autologous setting. Mobilized PBSC were enriched to mononuclear cells (MNC) by Percoll separation and then frozen at cell concentrations of 2-5 x 10(7)/ml (group I, n=20) or 2 x 10(8)/ml (group II, n=44) without the use of a programmed freezer using 5% DMSO, 6% hydroxy ethyl starch, and 4% autologous serum or human albumin. CD34+ cells purified by ISOLEX300 were frozen at 2 x 10(7)/ml (group III, n=22) using the same method. The median recovery rates of CD34+ cells and CFU-GM were, respectively, n.d. (not determined) and 88% in group I, 103 and 64% in group II, and 98 and 53% in group III. There was a statistical significance between the recovery rate of CFU-GM in group III and that in group I ( p=0.02). The median percentage of cell viability after thawing in each group was 89, 87, and 75%, respectively. The median numbers of days after PBSCT to achieve a WBC of >1.0 x 10(9)/l, an absolute neutrophil count of >0.5 x 10(9)/l, and a platelet count of >50 x 10(9)/l were, respectively, 11, 11 and 15 in group I; 12, 12 and 16 in group II; and 12, 12 and 27 in group III. These results suggest that enriched MNC from mobilized PBSC could be frozen at a higher cell concentration (2 x 10(8)/ml) without the use of a programmed freezer, leading to reduction of the toxicities associated with infusion of thawed cells and of costly space required for cell storage.