Reappraisal of endometrial thickness for the detection of endometrial cancer in postmenopausal bleeding: a retrospective cohort study.

OBJECTIVE: To estimate the accuracy of transvaginal ultrasound (TVS) measurement of endometrial thickness (ET) in diagnosing endometrial cancer in postmenopausal women with vaginal bleeding (PMB). DESIGN: Retrospective cohort study. SETTING: One-stop PMB clinic in a Hong Kong teaching hospital. POPULATION: A cohort of 4383 women with PMB. METHODS: Transvaginal ultrasonic measurement of ET and endometrial biopsies were obtained in women presenting with PMB between 2002 and 2013. Endometrial histology was used as the reference standard to calculate accuracy estimates. MAIN OUTCOME MEASURES: Accuracy data for TVS ET presented as sensitivity, specificity, and area under the receiver operator characteristic (ROC) curve. RESULTS: Endometrial cancer was diagnosed in 3.8% of women. The median ET in those with endometrial cancer was significantly higher than those with benign conditions (15.7 versus 3.2 mm, P < 0.001). The area under the ROC curve was 0.92 (95% CI 0.89-0.94). The sensitivity for the detection of endometrial cancer at 3-, 4-, and 5-mm cut-offs were 97.0% (95% CI 94.5-99.6%), 94.1% (95% CI 90.5-97.6%), and 93.5% (95% CI 89.7-97.2%), respectively. The corresponding estimates of specificity at these thresholds were 45.3% (95% CI 43.8-46.8%), 66.8% (65.4-68.2%), and 74.0% (72.7-75.4%). CONCLUSIONS: Transvaginal ultrasound using a 3-mm cut-off has high sensitivity for detecting endometrial cancer and can identify women with PMB who are highly unlikely to have endometrial cancer, thereby avoiding more invasive endometrial biopsy.

Menstrual problems and health-seeking behaviour in Hong Kong Chinese girls.

OBJECTIVE: To ascertain the prevalence of menstrual problems in adolescent girls and their health-seeking behaviour. DESIGN: Questionnaire survey on menstruation, menstrual problems, medical consultation, and factors influencing girls seeking medical care. SETTING: Secondary schools in the catchment area of a tertiary teaching hospital in Hong Kong. PARTICIPANTS: A total of 5609 girls from 10 secondary schools. MAIN OUTCOME MEASURES: Prevalence of menstrual problems and health-seeking behaviour of adolescent girls. RESULTS: The mean age of the girls and their mean age at menarche were 15.1 (standard deviation, 2.0) years and 12.3 (1.1) years, respectively. The prevalence of menorrhagia, dysmenorrhoea, and menstrual symptoms were 17.9% (95% confidence interval, 16.9-19.1%), 68.7% (67.7-70.3%), and 37.7% (36.7-39.3%), respectively. The prevalence of menstrual symptoms (P<0.001) and dysmenorrhoea (P<0.001) increased with gynaecological age (calendar age minus age at menarche), whilst the proportion having short or long cycles decreased (P=0.002 and P=0.009). One in eight girls reported having been absent from school, whilst only 6.4% had sought medical care because of menses. Multivariate analysis indicated that seeking medical care for menorrhagia was dependent on the opinion of a family member (P=0.005), and for dysmenorrhoea on its severity (P=0.046) and anxiety about embarrassing questions (P=0.039). CONCLUSIONS: The prevalence of menstrual problems in Hong Kong Chinese girls is high and causes significant disruption to their school and daily activities. However, only a minority seek medical advice.

A randomised controlled trial of prophylactic levonorgestrel intrauterine system in tamoxifen-treated women.

OBJECTIVE: To study the prophylactic use of levonorgestrel intrauterine system (LNG-IUS) in the prevention of endometrial pathology in women having breast cancer treated with tamoxifen. DESIGN: Randomised controlled trial. SETTING: A tertiary teaching hospital. POPULATION: One hundred and thirteen women (66 premenopausal/47 postmenopausal) who required adjuvant tamoxifen for breast cancer after the completion of postoperative radiotherapy and chemotherapy. METHODS: Women were randomised to treatment group (prophylactic LNG-IUS insertion before the commencement of tamoxifen) or control group. Uterine cavity was examined by outpatient hysteroscopy and endometrial biopsy before and at 12 months after commencement of tamoxifen. MAIN OUTCOME MEASURES: De novo endometrial pathology at 1 year of tamoxifen. RESULTS: Women in the treatment group had a much lower incidence of endometrial polyp (1.8 versus 15.5%, P= 0.017) (relative risk: 0.12; 95% CI: 0.02-0.91) at 12 months. There was no significant difference in the incidence of submucosal fibroid between the two groups (1.8 versus 3.4%, P= 1.0). LNG-IUS was retained in 95% women in the treatment group at 1 year. CONCLUSION: LNG-IUS reduces the occurrence of de novo endometrial polyp in women treated with tamoxifen for breast cancer.

An audit on hysterectomy for benign diseases in public hospitals in Hong Kong.

OBJECTIVE: To assess the standard of hysterectomy in public hospitals in Hong Kong, so as to improve the quality of patient care and outcome. DESIGN: Clinical audit. SETTING: Twelve Hong Kong Hospital Authority public hospitals. PATIENTS: All patients undergoing hysterectomy for benign gynaecological conditions during the period from 1 July 2002 to 31 December 2002 inclusive. RESULTS: A total of 1330 patients were included for analysis: 934 (70.2%) having abdominal hysterectomies, 184 (13.8%) having laparoscopic hysterectomies, and 212 (15.9%) undergoing vaginal hysterectomies. Uterine fibroids constituted the commonest indication for abdominal (73.7%) and laparoscopic (61.4%) hysterectomies, while genital prolapse was the most common indication (96.2%) for vaginal hysterectomy. The majority of patients undergoing laparoscopic and vaginal hysterectomy (86.3% and 84.8% respectively) were given prophylactic antibiotics, in contrast to only 45.8% of those undergoing abdominal hysterectomy. In all, 85.8% of the abdominal and vaginal hysterectomies performed by trainees were supervised, while for trainees performing laparoscopic hysterectomy, all had specialists as their first assistant. The overall incidence of complications for vaginal hysterectomy was lower than that for both abdominal hysterectomy (P<0.001) and laparoscopic hysterectomy (P<0.05). Infectious morbidity was significantly higher in patients undergoing abdominal hysterectomy without prophylactic antibiotics. CONCLUSION: The overall incidence of complications was lower for vaginal hysterectomies, as compared to both abdominal and laparoscopic hysterectomies, whereas the risk of urinary tract injury was significantly higher for laparoscopic hysterectomy. According to our audit, the level of supervision for the trainees was high. However, routine antibiotic prophylaxis should be more consistently used in the territory.

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.

Bone mineral density in children with thalassaemia major: determining factors and effects of bone marrow transplantation.

Osteoporosis and osteopenia affect up to half of patients with thalassaemia major (TM). We investigate the effects of acquired factors and BMT on bone mineral density (BMD) in these patients. In all, 53 patients on regular transfusion (BT group) and 33 patients at 5.7+/-1.9 years post transplant (BMT group) were recruited. BMD was measured by dual energy X-ray absorptiometry. Serum concentrations of osteocalcin, bone-specific alkaline phosphatase (ALP), beta-crossLap and urinary cross-linking deoxypyridinoline (DPD) were measured by chemiluminescence and enzyme immunoassay, respectively. Severe BMD deficit (Z-score <-2.5) at spine and hip were noted in 62 and 35% of BT group. Serum osteocalcin (beta=-0.463; P=0.006) was predictive of spine BMD, whereas age (beta=-0.843; P=0.007) and urine DPD (beta=-0.439; P=0.037) were associated with hip BMD in BT group. Among BMT patients, post transplant duration (beta=0.450; P=0.009) and serum bone-specific ALP (beta=-0.495; P=0.013) were associated with spine BMD. Severe BMD deficit was less common among BMT than BT patients (6 vs 35%; P=0.036). The mean (s.d.) osteocalcin levels in BMT and BT groups were 96.4 (72.7) microg and 68.9 (40.3) microg/l, respectively (P=0.037). In conclusion, severe BMD deficit is common in Chinese TM patients and BMT may reverse BMD deficit in these patients.

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.

Cord blood collection before and after placental delivery: levels of nucleated cells, haematopoietic progenitor cells, leukocyte subpopulations and macroscopic clots.

The number of nucleated cells infused into the recipient of a cord blood (CB) transplant has emerged as the most important factor affecting the probability and speed of engraftment. At present, there is no international consensus on the procedure of CB collection in the maternity ward. In order to maximise the yield of viable cells in a CB unit, we aimed to investigate the efficiency of CB collection, with respect to the time of delivery of the placenta. We analysed stem and progenitor cells in terms of CD34+ cell content and colony-forming activities, lymphocyte subpopulations and the presence of macroscopic clots in 93 paired CB samples, collected before and after the delivery of the placenta. Our results demonstrated that the median concentrations of nucleated cells and total colony-forming unit (CFU) were significantly lower in CB collected after placenta delivery by 9.5% (P < 0.001) and 11.6% (P = 0.015), respectively, when compared to their counterparts collected before placental delivery. A reduction of granulocytes (P < 0.001), monocytes (P < 0.001) and CD19+ B lymphocytes (P = 0.031) was observed, with no significant change in the proportion of T cell subsets (CD4+, CD8+ cells) or activated T cells (CD25+, CD45RO+ cells) in samples collected after placenta delivery. The incidence of macroscopic clots was also higher in these samples (31% vs 1%, P < 0.001). The reduction of stem and progenitor cells correlated significantly with that of major cell populations, indicating a general cell loss, possibly due to clotting activities developed with time. Our study has documented strong evidence for recommending the collection of CB before the delivery of the placenta.

Paecilomyces varioti fungemia in a bone marrow transplant patient.

Paecilomyces varioti, a fungus resembling penicillium spp, has been described in conjunction with impaired host defence or foreign body implants. We report a case of Paecilomyces varioti catheter-related fungemia that occurred during neutropenia in an allogeneic BMT patient receiving antifungal prophylaxis with fluconazole. Successful treatment was achieved by removal of central venous catheter, intravenous amphotericin B and oral itraconazole.

Human herpesvirus-6 encephalitis after unrelated umbilical cord blood transplant in children.

Three children developed human herpesvirus-6 (HHV-6), variant B encephalitis after unrelated umbilical cord blood transplant, in a single center. They developed clinical manifestations of encephalitis around day 17 post transplant. Impairment of consciousness, incoherent speech, episodic focal pruritus, motor weakness, convulsions and severe hyponatremia were features at presentation. Radiological investigation of brain ranged from unremarkable to extensive white matter and meningeal lesions. Diagnosis was established by the presence of HHV-6 DNA in cerebrospinal fluid (CSF). Retrospective analyses of plasma revealed the presence of viral DNAemia prior to the onset of disease in two subjects. Treatment with ganciclovir or foscarnet was given. Two subjects did not achieve engraftment and died of other transplant-related complications on day 38 and 56 post-transplant, respectively. One subject achieved disease-free survival for more than 1 year with a satisfactory neurological outcome. In conclusion, HHV-6 encephalitis is not uncommon among patients undergoing umbilical cord blood transplantation. It is worth conducting further studies on early diagnosis and optimal management of this potentially fatal disease.

Ex vivo expansion of enriched CD34+ cells from neonatal blood in the presence of thrombopoietin, a comparison with cord blood and bone marrow.

Neonatal blood (NB) contains substantial numbers of stem and progenitor cells which decline rapidly after birth. Using a combination of cord blood (CB) and NB, we performed a successful, sibling transplant for a thalassaemia patient, leading to the proposal that NB could be used as an adjunct to CB for transplantation. This study was aimed at addressing the feasibility of expanding NB and thus minimizing the volume needed from a NB collection. In the presence of early acting cytokines interleukin-1beta (IL-1beta), IL-3, IL-6, stem cell factor (SCF), flt-3 ligand with and without thrombopoietin (Tpo), we compared the expansion capacity of CD34+ enriched cells from CB, NB and bone marrow (BM). Flow cytometry and colony-forming unit (CFU) analyses show that Tpo significantly increased the expansion of CD34+ cells from CB and NB to early and committed progenitors. No significant difference was observed between the expansion of CB and NB at 7, 14 or 21 days of culture in terms of CFU, CD34+ and CD61+ cell subsets. The expansion capacity of BM was significantly lower than that of NB or CB, possibly related to the low proportion of CD34+ CD38- cells observed at day 0. There was a relatively rapid expansion of NB which was evident at day 7 whilst the expansion of CB and BM remained low, suggesting a speedy maturation process in the postnatal infant. The expanded cells, being heterogeneous in their morphology and cell surface marker expression, were mostly of the myeloid lineage (CD45+, CD33+ and HLA-DR+). Our results showed that the expansion capacity of NB is comparable to that of CB and if transplanted, the expanded products of NB might contribute to the engraftment kinetics of the neutrophil and megakaryocyte lineage.

Busulphan level and early mortality in thalassaemia patients after BMT.

The aim of the study was to correlate busulphan (BU) levels of thalassaemia patients with outcome of allogeneic transplant. BU levels were measured by gas chromatography mass fragmentography. All patients received a standardised dose of BU 16 mg/kg, and cyclophosphamide 150 or 200 mg/kg. For area-under-the-curve analysis (AUC), blood samples were obtained at 0, 1, 2, 3, 4 and 6 h after the first and fifth dose for all patients, and additional levels were measured after ninth and/or 13th dose in most patients. Outcome parameters examined included veno-occlusive disease of liver (VOD), idiopathic interstitial pneumonitis, chimerism, and day 90 survival. Twenty consecutive thalassaemia patients who underwent haematopoietic stem cell transplantation were studied. The median age at transplant was 11.2 years (range 3-21 years). Mean BU AUC levels were correlated with age at transplant (r = 0.58, P = 0.007). Nine patients developed VOD and six had mixed chimerism, but these did not correlate with mean BU AUC level. Four patients died before day 50 from VOD and interstitial pneumonitis. Patients with BU AUC levels greater than the median (908 micromol x min/l) had significantly lower probability of survival at day 90 (60%), whereas patients with BU AUC level less than the median all survived beyond day 90. No patient had graft rejection. In conclusion, a high BU AUC level was associated with a higher treatment-related mortality in thalassaemia patients after transplant.

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.

Cobblestone area-forming cells, long-term culture-initiating cells and NOD/SCID repopulating cells in human neonatal blood: a comparison with umbilical cord blood.

Our prior study demonstrated that neonatal blood (NB) contained hematopoietic stem and progenitor cells that declined rapidly after birth. To validate that NB is a source of functional stem cells, we characterized this population in terms of cobblestone area-forming cells (CAFC), long-term culture-initiating cells (LTC-IC) and NOD/SCID mouse repopulating cells (SRC) in NB and umbilical cord blood (CB). Our data demonstrated that the frequencies of CAFC (30.2 vs 37.1, P = 0.14) and LTC-IC (28.6 vs 31.0, P = 0.49) in 1 x 10(5) mononuclear cells (MNC) of NB and CB were similar, suggesting that these cells were preserved in the circulation of the neonates shortly after birth. Sublethally irradiated NOD/SCID mice were transplanted with CD34(+) cells enriched from thawed NB and CB. At 6 weeks post transplant, human (hu)CD45(+) cells were detected in the bone marrow (BM), spleen and peripheral blood (PB) of the mice as demonstrated by flow cytometric and DNA analysis. Levels of huCD45(+)cells and colony forming units (CFU) appeared to be dependent on the infusion cell dose and were higher in animals receiving CB cells when compared with those of the NB group. The transplanted cells were capable of differentiation into multi-lineage progenitor cells (CD34(+) cells and differential CFU), as well as mature myeloid (CD14(+), CD33(+)), B lymphoid (CD19(+)) and megakaryocytic (CD61(+)) cells in the recipients. NB cells, subjected to ex vivo culture in an optimized preclinical condition, were significantly expanded to early and committed progenitor cells. Expanded NB contained SRC at a reduced quantity but with high proportions of CD14(+) cells and CD33(+) cells. Our study confirms that NB contains pluripotent hematopoietic stem and progenitor cells capable of homing and engrafting the NOD/SCID mice.

A fludarabine-based conditioning regimen for severe aplastic anemia.

Graft rejection is a common problem after alternative donor transplantation for patients with refractory severe aplastic anemia (SAA). Intensification of the conditioning regimen, with the inclusion of irradiation, has often been advocated to combat this problem. With this approach engraftment rate improved, but the incidence of transplant-related complications is also increased, resulting in little change in the overall outcome. We investigated the use of the combination of fludarabine, cyclophosphamide and anti-thymocyte globulin as the conditioning regimen in five multiply-transfused SAA patients. Three patients received an HLA one-antigen disparate related donor transplant, while two patients were given marrow from matched, unrelated donors. The regimen was well tolerated, with only grade I toxicity encountered. With a median follow-up of 9 months, all patients are alive with complete donor chimerism. We conclude that fludarabine may be used in place of irradiation to augment the conditioning regimen of cyclophosphamide and anti-thymocyte globulin for alternative donor transplantation in children with SAA.

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.

Incidence, risk factors and outcome of varicella-zoster virus infection in children after haematopoietic stem cell transplantation.

We report a retrospective analysis of VZV infection after haematopoietic stem cell transplantation (HSCT) in children. Thirty-three (30%) of the total 109 children who were transplanted during a 7 year period developed post-transplant VZV infection. Twenty-four of these 33 (73%) children had VZV infection within 1 year following HSCT. The cumulative incidences of post-transplant VZV infection at 1 and 5 years were 26% and 45%, respectively. The positive and negative predictive values of pretransplant VZV serology in recipients on the development of HZ following HSCT were 39% and 88%, respectively. Pretransplant VZV seropositivity in recipients was the only risk factor for post-transplant herpes zoster (HZ) infection on multivariate analysis. All patients responded to acyclovir. The median duration of VZV infection was 5 days. Three (11%) and one (3%) children with HZ developed visceral dissemination and post-herpetic neuralgia, respectively. No mortality was directly attributed to VZV infection. VZV infection remains a major cause of morbidity in children after HSCT. Further studies are warranted to evaluate the potential use of VZV vaccine in these children. Bone Marrow Transplantation (2000) 25, 167-172.

Early iron reduction programme for thalassaemia patients after bone marrow transplantation.

Thirty thalassaemia patients received iron reduction starting at around 3 months post transplant. Sixteen received desferrioxamine and nine had phlebotomy, five patients had desferrioxamine followed by phlebotomy. The desferrioxamine group had higher serum ferritin levels at the start of iron reduction as compared to the phlebotomy group (5292 vs 2453 microg/l, P EQ 0.001). After 444 and 407 days of iron reduction, serum ferritins at cessation of iron reduction in both groups was similar (665 vs 588 microg/l). The rate of decline of serum ferritin in both groups was similar. There was no graft rejection during the programme. Early institution of iron reduction in ex-thalassaemia is safe.

Isolated testicular relapse after bone marrow transplant with total body irradiation and testicular boost in acute lymphoblastic leukemia.

A 7-year-old boy with Ph+ ALL received an allogeneic BMT in second remission. Conditioning included cyclophosphamide 60 mg/kg for 2 days, TBI 2 Gy twice daily for 3 days (12 Gy) and a single testicular boost of 4 Gy. He remained in hematological remission after BMT but developed isolated testicular relapse at 17 months. He underwent orchiectomy of the affected testis, 24 Gy testicular radiotherapy and systemic chemotherapy. He remains in remission 24 months after the testicular relapse. This is the first report of isolated testicular relapse which received a testicular irradiation boost included in the conditioning.

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.