Palliative Liver Radiotherapy (RT) for Symptomatic Hepatocellular Carcinoma (HCC).

This study aims at evaluating the symptom response, response duration, and toxicity of single dose palliative liver radiotherapy (RT) for symptomatic HCC patients. We reviewed unresectable HCC patients treated with palliative RT in our institution. Eligible patients were unsuitable or refractory to trans-arterial chemoembolization (TACE) and stereotactic body radiotherapy (SBRT), with an index symptom of pain or abdominal discomfort. The primary outcome was the percentage of patients with clinical improvement of index symptom at 1 month. Secondary outcomes were response duration, toxicities, alpha-feto protein (AFP) response, and radiological response. Fifty-two patients were included in the study. The index symptom was pain in 34 patients (65.4%), and abdominal discomfort (34.6%) in 18 patients. At 1 month, 51.9% of patients had improvement of symptoms. Median time to symptom progression was 89 days (range: 12-392 days). Treatment was well tolerated with only 2 patients (3.8%) developing grade 3 GI toxicities. AFP response, radiological response rate, and disease control rate at 3 months were 48.6%, 15.1%, and 54.5% respectively. Half of the patients had improvement of index symptoms after receiving palliative liver RT with median response duration of 3 months. The treatment was well tolerated with minimal toxicities.

Indiscernible benefit of high-resolution HLA typing in improving long-term clinical outcome of unrelated umbilical cord blood transplant.

The success of allogeneic hematopoietic stem cell transplantation depends in part on the accuracy of human leukocyte antigen (HLA) matching between the donor-recipient pair. The higher the number of matching HLA alleles, the smaller the chance that the transplant recipient will develop complications. Umbilical cord blood (UCB) transplantation was noted to result in a remarkably low frequency and severity of graft-versus-host disease (GvHD) and graft rejection compared to that in unrelated bone marrow transplant recipients. At present most banks match UCB donors for respective recipients by HLA-A, -B low-resolution typing and -DRB1 high-resolution typing. We retrospectively conducted high-resolution sequence-based HLA typing on DNA samples available from 65 Chinese UCB-recipient pairs typed previously by using low-resolution sequence-specific oligonucleotide probes and sequence-specific primers, and evaluated the clinical outcome. High-resolution typing revealed imperceptible HLA alleles that were hardly identified in low-resolution typing. Univariate analyses demonstrated no significant correlation between the extents of high-resolution HLA disparity with engraftment, graft failure, acute GvHD, transplant-related mortality and long-term 6-year overall survival. Data from the study suggest that high-resolution typing for HLA-A, -B and -DRB1 contributed no substantial improvement to UCB transplant outcome. Low-resolution typing appears to be amenable to matching UCB-recipient pairs without compromising the quality of transplant.

Multipotent neural precursors express neural and hematopoietic factors, and enhance ex vivo expansion of cord blood CD34+ cells, colony forming units and NOD/SCID-repopulating cells in contact and noncontact cultures.

In view of the possible crosstalks between hematopoiesis and neuropoiesis, we evaluated two microenvironments, murine neonatal neural cell line C17.2 and primary embryonic aorta-gonad-mesonephros (AGM) stromal cells, on the ex vivo expansion of CD34+ cells from human cord blood. In a contact culture system, C17.2 or AGM cells significantly enhanced the expansion of CD34+ cells to a panel of early and committed hematopoietic progenitor cells. In a noncontact transwell system, pre-established C17.2 cells significantly increased the expansion of total nucleated cells, CD34+ cells and multilineage colony forming cells (P<0.01). Expanded cells were infused into nonobese diabetic/severe-combined immunodeficient mice. The engraftment of human (hu)CD45+ cells in the bone marrow of these mice was consistently higher in all the 10 experiments conducted with the support of C17.2 cells when compared with those in respective control groups (11.9 vs 2.43%, P=0.03). Using RT-PCR and Southern blot analysis, we showed that AGM and C17.2 cells expressed a panel of hematopoietic, bone morphogenetic and neurotrophic factors. Our data provided the first evidence on the promoting effects of a neural progenitor cell line on hematopoiesis at a noncontact condition. The mechanism could be mediated by the expression of multilineage regulatory factors.

Migration of bone marrow stem cells in ischaemic brain.

Stem cell therapy has been demonstrated to be effective in the management of haematological malignancy and solid cancer, but its role in neurodegenerative conditions remains uncertain. We hypothesize that: (1) ventricular delivery of bone marrow stem cells improves functional outcome in experimental ischaemia of the mouse brain; and (2) this improved outcome is due to migration of bone marrow stem cells to areas of ischaemia. Twelve mice with transient cerebral hemisphere ischaemia were randomly allocated to receive bone marrow stem cells or saline. The six animals that underwent cell therapy were found to perform better and committed fewer errors in the water maze system compared with the six control mice. Migration of these bone marrow stem cells was evident within the ventricular cerebro-spinal fluid (CSF) system and the brain parenchyma. This could also occur in clusters of cells. Preferential migration of these cells took place in lesioned areas.

Frequent death-associated protein kinase promoter hypermethylation in multiple myeloma.

UNLABELLED: Death-associated protein (DAP) kinase is a novel gene regulating apoptosis induced by IFN-gamma. In B-cell malignancies, loss of DAP kinase expression is commonly associated with promoter hypermethylation. These characteristics of DAP kinase may be of particular relevance in multiple myeloma (MM), a B-lineage malignancy in which prolonged survival capacity of the malignant plasma cells may be critical in the induction and maintenance of tumor cells. PURPOSE: The involvement and potential role of DAP kinase in MM pathogenesis was examined. EXPERIMENTAL DESIGN: In this investigation, methylation-specific PCR was conducted on primary MM and MM cell lines. Methylation status findings were correlated with clinical parameters. RESULTS: We first demonstrated frequent DAP kinase hypermethylation in 24 of 36 primary MMs (20 of 26 at diagnosis and 4 of 10 with relapse/residual MM after treatment), 1 of 2 patients with monoclonal gammopathy of undetermined significance, and 1 of 3 MM cell lines studied. The high frequency of DAP kinase hypermethylation was similarly observed in MM of different stages, immunoglobulin isotypes, and histological grades, with or without plasmacytomas. Although not statistically significant, the overall survival of patients with DAP kinase methylation was notably shortened among 23 MM patients followed prospectively (P = 0.38 by Kaplan-Meier method and log-rank test). This preliminary finding suggests prognostic implications of DAP kinase in MM that may deserve further investigation. CONCLUSIONS: Our data suggest an important role for DAP kinase in MM tumorigenesis.

Granulocyte colony-stimulating factor-mobilized peripheral blood stem cells in beta-thalassemia patients: kinetics of mobilization and composition of apheresis product.

beta-Thalassemias are often associated with bone marrow expansion and immunomodulation in terms of lymphocyte subsets and cytokine levels in the peripheral blood. The mobilization of peripheral blood stem cells (PBSC) by cytokines in such a background has not been reported. If achieved, the apheresis product could be used as a stem cell back-up for beta-thalassemia patients prior to bone marrow transplant. PBSC collection may also become a means for providing stem and progenitor cells for gene manipulation and therapy of this disorder. The aim of the study was to assess the administration of G-CSF in mobilizing stem and progenitor cells in these patients and to compare the kinetics of CD34+ cells and lymphocyte subsets with those of healthy PBSC donors. Results showed that the CD34+ cells were effectively mobilized by G-CSF (10-16 micrograms/day per kg) in 20 thalassemia patients and 11 healthy donors. Although no significant difference was observed in levels of daily stem cell counts between the two groups of subjects, a 1 day delay in achieving peak levels of CD34+ cells was observed in the majority of thalassemia patients. The peak increase of CD34+ cells was 21.5 +/- 6.1-fold and 30.8 +/- 7.6-fold of the basal steady-state levels in thalassemia patients and healthy donors, respectively. Similar to the situation of healthy donors, G-CSF stimulated essentially the CD34+ cells and the myeloid lineage (granulocytes, monocytes) in thalassemia patients and had a slight effect on lymphocyte subsets (T-helper, T-suppressor, NK, and B cells) and activation (CD25, HLA-DR, and CD45RO). Compositions of the apheresis products, including CD34+CD38-, CD34+CD33+ and CD34+HLA-DR- cells, were similar in the two groups of subjects. Correlation studies showed that the level of CD34+ cells in the PB is a good indicator of that in the apheresis product (r = 0.88, p < 0.001). The study has demonstrated that under close monitoring of CD34+ cell levels in PB, the mobilization by G-CSF and collection of PBSC in beta-thalassemia patients are feasible.

Transfusion of peripheral blood stem cells from donor homozygous for a shared HLA-haplotype: avoiding fatal transfusion-associated graft-versus-host disease while preserving anti-leukemic effect.

BACKGROUND: Fatal transfusion-associated graft-versus-host disease was observed in immunocompetent patients transfused with blood from donors homozygous for a shared haplotype with the recipient (the P-F1 barrier). We tested whether it was possible to carry out successful transplantation in a patient with relapsed acute myeloid leukemia, using peripheral blood stem cells from his HLA-homozygous brother (HLA A2, B46, DRB1 901) who shared a haplotype with the patient (HLA A2, B46,75, DRB1 901,12). METHODS: A CD34 positively selected cell fraction (5.46x 10(6) CD34 cells/kg) was infused first, followed by subsequent infusion of graded doses of donor T cells (total 7.25x10(7) T cells/kg). Nonmyeloablative chemotherapy with idarubicin and cytarabine was given during the transplantation to reduce the leukemic burden and facilitate engraftment. Polymerase chain reaction with the VNTR primers, D1S80, was used to detect engraftment. RESULTS: Complete remission (>300days) and successful donor engraftment (90%) were achieved. CONCLUSIONS: Peripheral blood stem cells transplantation from a donor with a homozygous shared haplotype is possible with a minimal preparative regimen.

Recurrent chromosomal rearrangements involving breakpoints 3p21 and 19q13 in Chinese IgD multiple myeloma detected by G-banding and multicolor spectral karyotyping: a review of IgD karyotype literature.

Immunoglobulin D multiple myeloma (IgD MM) is a rare subtype that accounts for 1% to 3% of MM and shows higher aggressiveness with distinctive clinical and laboratory features. However, there is little information in the literature on their karyotypes, which are mainly derived from G-banding results. Our current study on 2 Chinese IgD MM thus represents the first description of cytogenetic data on this subtype based on an integrated analysis with G-banding and multicolor spectral karyotyping (SKY). Both of our cases showed some usual features of MM, as well as a few novel translocations including t(3;22), t(6;19), t(X;19) and the 3 whole-arm translocations namely t(1;6)(q10;p10), t(4;9)(q10;p10), and t(16;18)(q10;q10). We also identified recurrent chromosomal rearrangements involving breakpoints 3p21 and 19q13, which may suggest to be unique aberrations that may underline the pathogenesis of this distinctive biological MM subtype.

Umbilical cord blood transplantation for Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI).

Severe Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) is usually fatal by early adulthood. Bone marrow transplantation is the only form of definitive enzyme replacement therapy available. A 5-year-old boy with Maroteaux-Lamy syndrome has successful recovery of bone marrow and enzymatic functions after umbilical cord blood transplant from his unaffected HLA-identical brother. Busulphan (16 mg/kg) and cyclophosphamide (200 mg/kg) were used as preparative chemotherapy with short methotrexate and long cyclosporin as prophylaxis against graft-versus-host disease (GVHD). A total of 6.08 x 10(7)/kg nucleated cells and 2.92 x 10(5)/kg CD34+ cells were transplanted with neutrophil engraftment achieved on day 26. There was no evidence of acute and chronic GVHD. Fifteen months after transplant, a normal level of N-acetylgalactosamine-4-sulphatase activity was achieved despite mixed chimerism. There was clinical improvement of hepatosplenomegaly, facial and skin features, joint mobility and resolution of suppurative middle ear effusion. He returned to school and continued to perform well in academic studies. We report here the first successful umbilical cord blood transplant as treatment of Maroteaux-Lamy syndrome.

A more immunosuppressive pre-transplant conditioning may be required for Chinese patients with thalassaemia.

Bone marrow transplantation was performed on 14 Chinese patients with transfusion dependent thalassaemia major (n = 13) and haemoglobin H disease (n = 1). The donors were HLA identical siblings. The source of haematopoietic stem cells were from bone marrow (n = 13) and umbilical cord blood (n = 1). The pre-transplant conditioning regimens were (1) busulphan 14 mg/kg and cyclophosphamide 200 mg/kg in two patients; (2) busulphan 16 mg/kg, cyclophosphamide 200 mg/kg and anti-thymocyte globulin 110 mg/kg in five patients; (3) busulphan 16 mg/kg, cyclophosphamide 150 mg/kg and anti-thymocyte globulin 110 mg/kg in seven patients. Graft-versus-host disease prophylaxis was cyclosporin A and methotrexate. All patients engrafted and achieved stable haematopoiesis except the one who underwent the umbilical cord blood transplant, who had autologous marrow recovery. One patient who had stable engraftment rejected the marrow graft and developed aplastic anaemia 4 months after BMT. This patient had a second BMT but rejection recurred again. She eventually died of septicaemia. The other 12 patients were transfusion independent and disease free. The majority have gone back to school or work. Disease-free and actuarial survival probability were 85 and 93%, respectively with a median follow-up time of 30 months (13 to 42 months). Our data suggest that BMT from HLA identical siblings for transfusion dependent thalassaemia gives a high chance of cure with acceptable mortality and morbidity, and that a more immunosuppressive pre-transplant conditioning schedule may be required to prevent rejection.

Platelet-derived growth factor enhances ex vivo expansion of megakaryocytic progenitors from human cord blood.

Infusion of ex vivo expanded megakaryocytic (MK) progenitor cells is a strategy for shortening the duration of thrombocytopenia after haematopoietic stem cell transplantation. The cell dose after expansion has emerged as a critical factor for achieving the desired clinical outcomes. This study aimed to establish efficient conditions for the expansion of the MK lineage from enriched CD34(+) cells of umbilical cord blood and to investigate the effect of platelet-derived growth factor (PDGF) in this system. Our results demonstrated that thrombopoietin (TPO) alone produced a high proportion of CD61(+)CD41(+) cells but a low total cell count and high cell death, resulting in an inferior expansion. The addition of interleukin-1 beta (IL-1 beta), Flt-3 ligand (Flt-3L) and to a lesser extent IL-3 improved the expansion outcome. The treatment groups with three to five cytokines produced efficient expansions of CFU-MK up to 400-fold with the highest yield observed in the presence of TPO, IL-1 beta, IL-3, IL-6 and Flt-3L. CD34(+) cells were expanded by five to 22-fold. PDGF improved the expansion of all cell types with CD61(+)CD41(+) cells, CFU-MK and CD34(+) cells increased by 101%, 134% and 70%, respectively. On day 14, the CD61(+) population consisted of diploid (86.5%), tetraploid (11.8%) and polyploid (8N--32N; 1.69%) cells. Their levels were not affected by PDGF. TPO, IL-1 beta, IL-3, IL-6, Flt-3L and PDGF represented an effective cytokine combination for expanding MK progenitors while maintaining a moderate increase of CD34(+) cells. This study showed, for the first time, that PDGF enhanced the ex vivo expansion of the MK lineage, without promoting their in vitro maturation. PDGF might be a suitable growth factor to improve the ex vivo expansion of MK progenitors for clinical applications.

Single vs twice daily G-CSF dose for peripheral blood stem cells harvest in normal donors and children with non-malignant diseases.

The optimal dose and schedule of G-CSF for mobilization of peripheral blood stem cells (PBSC) is not well defined. G-CSF mobilization was performed in a group of healthy donors and paediatric patients for autologous back-up before receiving allogeneic stem cell transplant. Seventeen consecutive subjects who received G-CSF at 5 microg/kg/dose twice daily (group A) were compared with a historical control group of 25 subjects who received a single daily dose of 10 microg/kg/day G-CSF (group B). Double blood volume apheresis for PBSC collection was started on day 5. G-CSF was continued and apheresis repeated until the targeted CD34+ cell dose was achieved. Both groups were comparable for sex, age, body weight and reason for PBSC collection. Over two-thirds of the subjects in both groups were less than 16 years of age. The G-CSF priming and apheresis were well tolerated. When the first day apheresis products were analyzed, group A resulted in significantly higher yield of total nucleated cells (5.91 vs 3.92 x 108/kg, P = 0. 013), mononuclear cells (5.73 vs 3.92 x 108/kg, P = 0.017), CD34+ cells (2.80 vs 1.69 x 106/kg, P = 0.049) and colony-forming units (107 vs 54 x 104/kg, P = 0.010) as compared with group B. We conclude that the two dose schedule is more efficient in mobilizing PBSC in normal donors and children with non-malignant diseases. This approach may reduce the number of aphereses required and thus reduce the transplant cost.

Lymphocyte subsets and natural killer cell cytotoxicity after laparoscopically assisted resection of rectosigmoid carcinoma.

BACKGROUND: Laparoscopically assisted resection of colorectal carcinoma is technically feasible and minimally invasive. Postoperative immunosuppression also may be reduced. This study compared the lymphocyte subsets and natural killer (NK) cell cytotoxicity in patients after laparoscopically assisted resection with those after open resection of rectosigmoid carcinoma. METHODS: In this study, 40 patients with rectosigmoid carcinoma, but no evidence of metastasis, were randomized to receive either laparoscopically assisted or conventional open resection of the tumor. Blood was collected before the operation, then 24 h, 72 h, and 8 days after the operation for studies of lymphocyte subsets and NK cell cytotoxicity. RESULTS: The lymphocyte subsets and NK cell cytotoxicity of both groups showed typical suppression after surgery. The suppression of T cell activation and NK-like T cells was significantly less after laparoscopically assisted resection than in after open resection, whereas the difference in other lymphocyte subsets and NK cell cytotoxicity was not significant. CONCLUSION: This study showed that some cellular components of the immune system are less suppressed after laparoscopically assisted than after conventional open resection of rectosigmoid carcinoma. This may have implications for tumor recurrence and long-term patient survival.

Unrelated umbilical cord blood transplantation in children: experience of the Hong Kong Red Cross Blood Transfusion Service.

OBJECTIVE: To review the outcome of unrelated umbilical cord blood transplantation in children using cord blood from the Hong Kong Red Cross Blood Transfusion Service. DESIGN: Retrospective study. PATIENTS: Records of eight patients who received unrelated umbilical cord blood transplants between 1999 and 2003 were reviewed. MAIN OUTCOME MEASURES: Engraftment of haematopoietic cells and graft-versus-host disease after transplantation. RESULTS: The median age of the patients was 4.9 years (range, 1.0-9.4 years). Five patients had acute leukaemia, one had non-Hodgkin's lymphoma, one had X-linked adrenoleukodystrophy, and one had mucolipidosis. The infused umbilical cord blood units contained a median of 6.7 x 10(7) /kg nucleated cells and 4.0 x 10(5) /kg CD34-positive cells. Neutrophil engraftment was achieved at a median of 13 days (range, 11-19 days) and, for seven patients, platelet engraftment was achieved at a median of 39 days (range, 24-98 days). Acute graft-versus-host disease occurred in all patients (grades I to III). One of the patients died because of encephalitis; of the other seven, five developed chronic graft-versus-host disease of the skin. At a median follow-up of 2 years, the four patients with leukaemia and the one with non-Hodgkin's lymphoma remained in continuous complete remission; the patient with adrenoleukodystrophy showed stabilisation of neurological condition. CONCLUSION: The Hong Kong Red Cross Blood Transfusion Service Cord Blood Bank stored cord blood units of good quality for transplantation, the outcome of which was comparable to that of bone marrow transplantation.

HLA-B67 may be a male-specific HLA marker of susceptibility to relapsed childhood ALL in Hong Kong Chinese and HLA-A33 or HLA-B17 signifies a higher presentation leukocytosis: A retrospective analysis on 53 transplant candidates (1989-2003).

We performed a retrospective analysis on the human leukocyte antigen (HLA) data of 53 consecutive Chinese patients with high-risk childhood acute lymphoblastic leukemia (ALL) diagnosed from 1989 to 2003. A significantly higher frequency of HLA-B67 in the male relapse group of patients [OR, 23.08; 95% CI, 5.31-100.36; p = 0.0042; for statistical significance after Bonferroni correction (Bc) p (Bc) < 0.0083] was identified after Bonferroni correction. Although not surviving the Bonferroni correction, gender effects on the association were also observed with HLA-A11, HLA-A32, HLA-A33, and HLA-B22, which were however more prevalent in the female patients and particularly those developing relapse. Two patients with HLA-A29 and HLA-B7 revealed significantly shortened survivals, suggestive of their potential prognostic impacts. Notably, for the first time, we found a significant correlation of leukocyte count with HLA types, where HLA-A33 (p = 0.006) or HLA-B17 (p < 0.001) signifies higher leukocytosis at presentation. Taken together, our findings support the involvement of HLA in Chinese high-risk childhood ALL.

Banking and transplantation of umbilical cord blood in Guangzhou, China.

BACKGROUND: Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells (HSC) for transplantation of patients with hematologic malignancies or hereditary diseases. METHODS: We developed a provincial UCB bank in Guangzhou, China, using good manufacturing practices and standard operating procedures to address donor eligibility, collection, characterization, processing, storage and release from quarantine. The banking activities were analyzed. RESULTS: From June 1998 to May 2005, 8623 UCB units of Han ethnic origin were collected; 4147 (48.1%) were stored, while 4476 (51.9%) were discarded as a result of pre-determined exclusion criteria. A median volume of 95.5 mL (range 60-227.7) and 1.2 x 10(9) (0.8-9.3) nucleated cells were collected. The cell viability was 97.8% (90-100%). The CD34+ cell count of 3691 (89.0%) UCB units was 5.2 x 10(6) (0.3-131.6) and clonogenic assays of 4036 (97.3%) UCB units demonstrated 9.8 x 10(5) (0.04-135.8) CFU-GM, 0.3 x 10(5) (0.0-18.6) CFU-GEMM and 8.8 x 10(5) (0.0-74.2) BFU-E. A total of 0.4% (15/3863) UCB derived from babies known to have health problems at age 6 months was discarded. Up to May 2005, 151 units were issued for transplantation to 127 patients [90 (70.9%) children and 37 (29.1%) adults]. The infused nucleated cells in unrelated single-unit recipients were 3.4 x 10(7)/kg (1.7-14.9) for adults (n=19) and 5.7 x 10(7)/kg (2.0-20.5) for children (n=71), respectively. The numbers of days for the engraftment of neutrophils among 65 children and 22 adults were 17 (7-41) and 20 (10-42), respectively. DISCUSSION: Data of this study show that stringent procedures and comprehensive policies are requisite for pursuing the banking and release of quality UCB for successful transplantation.

Bone marrow transplantation for beta-thalassaemia major by an HLA-mismatched parent.

A six-year-old boy was diagnosed with beta-thalassaemia major during infancy. Since then, he required monthly blood transfusion and irregular iron chelation therapy. He had hepatosplenomegaly and elevated liver enzymes; the serum ferritin was up to 3800 ng/mL. An echocardiogram showed left-ventricular enlargement. His one-antigen-mismatched mother was chosen as a bone marrow donor. He was pretreated with intensive red blood cell transfusion and hydroxyurea for 6 weeks prior to conditioning. The conditioning included total body irradiation (300 cGy), busulfan (14 mg/kg), cyclophosphamide (160 mg/kg) and anti-thymocyte globulin (rabbit; 90 mg/kg). Marrow cell dose was 5.4 x 108/kg. Graft versus host disease (GVHD) prophylaxis included cyclosporine A (CSA) and methylprednisolone. Neutrophil engraftment occurred on day 23. Grade II acute GVHD occurred on day 45. The patient developed complications including septicaemia, haemorrhagic cystitis, intracranial haemorrhage and heart failure. He subsequently recovered from the complications without sequelae. The patient remained transfusion-independent at a follow-up examination after 18 months. This case suggested that a mismatched family member may be considered as a bone marrow donor for beta-thalassaemia major. In places where conventional treatment is not feasible, for example, in China, this approach may be an alternative option. A more intensive immunosuppressive regimen and a higher marrow cell dose may be important for successful engraftment. High-dose anti-thymocyte globulin may also prevent severe GVHD.

Allogeneic peripheral blood stem cell transplant in children.

Allogeneic peripheral blood stem cell (PBSC) transplant has recently been introduced for the treatment of hematological malignancies. As the data were limited mainly to adult patients, this study aimed to assess the feasibility and safety of this procedure in pediatric patients and donors. Eleven children aged 2-16 years received allogeneic PBSC transplant for acute lymphoblastic leukemia (n = 4), acute myeloid leukemia (n = 1), myelodysplastic syndrome (n = 1), severe aplastic anemia (n = 3), and thalassemia (n = 2). Nine donors were human leukocyte antigen (HLA)-identical siblings and the other two were one antigen mismatched family members. Eight donors were younger than 18 years old (10 months to 17 years). Donors were primed with granulocyte colony-stimulating factor (G-CSF) at 10-16 micrograms/kg for 4-5 days. Aphereses were performed on 1 or 2 consecutive days, and the patients received a mean of 14.4 x 10(8)/kg nucleated cells, 6.9 x 10(6)/kg CD34 cells, and 6.9 x 10(8)/kg T cells. All patients achieved neutrophil counts of > 0.5 x 10(9)/l at a median of 16 days. Nine patients achieved platelet counts of > 20 x 10(9)/l at a median of 13 days. Grade II acute graft vs. host disease (GVHD) occurred in only one patient. Chronic GVHD was not observed in the seven patients with follow-up of more than 3 months. Eight patients remained in continuous complete remission after transplant ranged from 2 to 26 months. Allogeneic PBSC transplant appears safe in pediatric patients and donors, and it seems not to be associated with increase of acute GVHD or chronic GVHD.

Treatment of hemoglobin Bart's hydrops with bone marrow transplantation.

A 21-month-old girl with hemoglobin Bart's hydrops received bone marrow transplantation (BMT) from a matched sibling. No major BMT-related complications developed. Hemoglobin levels remained greater than 10 gm/dl for 20 months without blood transfusion support despite the presence of residual host hemopoietic cells from 2 months after BMT. We suggest consideration of this therapeutic option for surviving patients.