The incidence, diagnostic clinical manifestations and severity of juvenile systemic lupus erythematosus in New Zealand Maori and Pacific Island children: the Starship experience (2000-2010).

OBJECTIVES: To describe the incidence, diagnostic clinical manifestations and severity of juvenile systemic lupus erythematosus (jSLE) in a cohort of New Zealand Maori and Pacific Island children compared to European children. METHODS: A chart review was conducted of children with jSLE seen by the Starship paediatric rheumatology and/or renal services between January 2000 and November 2010. Diagnostic clinical data and lupus nephritis data at anytime were collated while classic British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were derived retrospectively. RESULTS: Thirty-two children were diagnosed with jSLE with an annual incidence of 0.52 per 100,000 per year. Compared with European children (0.31 per 100,000 per year) the incidence of jSLE was higher among Maori and Pacific (0.67 per 100,000 per year, p=0.06) and significantly higher among Asian children (1.17 per 100,000 per year, p=0.01). Compared with European children, Maori and Pacific children were more frequently diagnosed with lupus nephritis (80% vs 40%, p=0.09) and severe (WHO class 4 or 5) renal lesions (60% vs 40%, p=0.43) at presentation. Similarly, at any time during the study, lupus nephritis (100% vs 40%, p=0.001) and severe (WHO class 4 or 5) renal lesions (73.3% vs 40%, p=0.12) were more frequent among Maori and Pacific compared with European children. Furthermore, retrospective BILAG assessment of diagnostic disease severity demonstrated that Maori and Pacific children experienced the majority of severe "Category A" disease (56.8% vs 22.7%, p=0.17) which was predominantly renal (73.3% vs 40%, p=0.12) in nature. CONCLUSIONS: This is the first description of the incidence and clinical manifestations of jSLE in a cohort of New Zealand children. Although limited by the small numbers involved it confirmed anecdotal suspicions that the incidence of jSLE among Maori, Pacific and Asian children is higher than European children. Lupus nephritis is also more frequent and severe in Maori and Pacific children.

Treatment of chronic myelogenous leukemia with allogeneic bone marrow transplantation after preparation with busulfan and cyclophosphamide (BuCy2): an update.

Allogeneic bone marrow transplantation (BMT) has been shown to result in long-term disease-free survival in patients with leukemia. However, the utility of this treatment approach is limited by treatment-related morbidity and mortality. We present an update of a study in which a BMT preparative regimen consisting of a 4-day course of busulfan and a 2-day course of cyclophosphamide (BuCy2) was used in patients with chronic myelogenous leukemia. Patient survival depended on disease stage, with a 58% survival rate for patients in first chronic phase, 41% for those in accelerated phase, and 25% for those in the blast transformation stage. There was a significant difference in patient survival between those who received transplants within 1 year of diagnosis and those who received transplants more than 1 year after diagnosis (70% v 40%). This difference appeared to be due to the extent of previous exposure to busulfan. The overall mortality rate in this study was 46%. We conclude that the BuCy2 preparative regimen is similar in effectiveness to regimens that include total body irradiation and results in comparable levels of transplant-related mortality. Our results strongly indicate that patients with chronic myelogenous leukemia who receive BMT within the first year after diagnosis have a significantly better clinical outcome than those who receive BMT later in the course of the disease.

Cyclosporin-associated central nervous system toxicity after allogeneic bone marrow transplantation.

Five of 64 recipients of HLA-identical sibling marrow allografts who were given cyclosporin (CSP) to minimize graft-versus-host disease posttransplant had a serious neurological illness thought to be due to CSP. Characteristic clinical features included a motor spinal cord syndrome, a cerebellar-like syndrome, and mental confusion. All five recovered when the CSP dose was reduced or the drug was stopped.

Late onset transfusion-dependent anaemia with thrombocytopenia secondary to marrow fibrosis and hypoplasia associated with chronic graft-versus-host disease.

Late onset transfusion-dependent anaemia is very rare in the presence of sustained engraftment after HLA-identical sibling bone marrow transplantation. The only previously described consistent cause is pyridoxine-responsive sideroblastic anaemia. We describe here a second cause, marrow hypoplasia and fibrosis, occurring in association with extensive chronic graft-versus-host disease (GVHD). A 20-year-old Caucasian male who received cyclophosphamide and fractionated total body irradiation followed by an unmanipulated HLA-identical sibling marrow transplant from his sister for acute nonlymphoblastic leukaemia in first remission developed chronic GVHD of the skin and mouth at day 101 post-transplant. At day 689 post-transplant, he developed leuco-erythroblastic anaemia with thrombocytopenia, due to patchy marrow hypoplasia and fibrosis. Between days 689 and 1987 post-transplant he received 71 units of packed red cells, requiring transfusion approximately monthly. He remains well although still on prednisone for chronic GVHD of skin and is receiving desferrioxamine 4 g five nights/week i.v. as prophylaxis for iron overload.

An acute pulmonary syndrome possibly representing acute graft-versus-host disease involving the lung interstitium.

An acute pulmonary syndrome possibly representing acute graft-versus-host disease (GVHD) involving lung interstitium occurred in a patient given an allogeneic bone marrow transplant for haematological malignancy. He presented at day 34 with acute GVHD of skin and bowel, and this was associated with cough, dyspnoea and an asymmetrical change on chest X-ray. Lung biopsy demonstrated an interstitial and peribronchial lymphocytic infiltrate and acute bronchial epithelial degeneration. He responded symptomatically to high dose intravenous methylprednisolone. The radiological change resolved completely. This case, thought to represent GVHD involving lung interstitium, emphasizes the need for tissue procurement in the management of non-bacterial lung disease after marrow transplantation.

Second marrow transplants for recurrence of haematological malignancy.

Nine patients with haematological malignancy relapsed 3-32 months after receiving cyclophosphamide 120 mg/kg, 12-14 Gy fractionated total body irradiation and an HLA-identical sibling bone marrow transplant. They were reconditioned with melphalan 180-220 mg/m2 and retransplanted using the same donor and the same cyclosporin regimen as prophylaxis for graft-versus-host disease (GVHD). Three of the nine remain alive greater than 81, greater than 33, and greater than 36 months after second transplant. While the rate of marrow engraftment, the incidence of acute GVHD and the incidence of interstitial pneumonitis were similar after first and second transplants, the use of melphalan before second transplant was associated with increased nephrotoxicity and oropharyngeal mucositis. The present study shows that second narrow transplants are feasible, can produce prolonged remission of haematological malignancies and should be considered in appropriate patients who relapse after first marrow transplant.

Bladder irrigation does not prevent haemorrhagic cystitis in bone marrow transplant recipients.

Thirty-four patients receiving allogeneic bone marrow transplants as treatment for haematological malignancy were prospectively randomized to receive or not to receive bladder irrigation by indwelling urinary catheter during preparation for transplant. Twenty-two patients received busulphan and cyclophosphamide, four received busulphan, cyclophosphamide and irradiation, and eight received cyclophosphamide and total body irradiation. The actuarial incidence of haemorrhagic cystitis in those randomized to receive bladder irrigation was 48% for the whole group and 52% in those receiving busulphan and cyclophosphamide only. In those randomized not to receive bladder irrigation the incidence of haemorrhagic cystitis was 29% for the overall group and 38% in those receiving busulphan and cyclophosphamide. There was no statistically significant difference between the two groups. We conclude that bladder irrigation does not minimize the risk of haemorrhagic cystitis in this patient population.

Recipients of HLA-identical sibling marrow transplants with severe aplastic anemia engraft more quickly, and those with chronic myeloid leukemia more slowly, than those with acute leukemia.

An analysis of the rate of leukocyte reconstitution in 164 recipients of HLA-identical sibling marrow transplants showed two factors to be independently influential. These were the underlying diagnosis and the type of prophylactic regimen used to minimize the risk of graft-versus-host disease. Patients with severe aplastic anemia had a faster rate of reconstitution of the total white blood cell count to levels of both 500 and 1000 x 10(6)/l than patients with acute non-lymphoblastic leukemia (ANL), acute lymphoblastic leukemia (ALL) or chronic myeloid leukemia (CML). Patients with severe aplastic anemia (SAA), however, did not show a faster rate of reconstitution of blood neutrophils. As well as being slower than patients with SAA for total leukocyte reconstitution, patients with CML were slower than patients with ANL and ALL in attaining a neutrophil count of 500 x 10(6)/l, and slower than patients with ANL in attaining a neutrophil count of 1000 x 10(6)/l. Patients given cyclosporin as the sole immunosuppressant prophylactic regimen post-transplant had faster reconstitution to total leukocyte counts of 500 and 1000 x 10(6)/l and to neutrophils of 1000 x 10(6)/l than patients given methotrexate alone, methotrexate and cyclosporin, or cyclosporin and T cell depletion of the donor marrow. No other factors (including the pretransplant preparative regimen) were significant in influencing the rate of leukocyte or neutrophil reconstitution. When only patients given cyclosporin were analysed, those with severe aplastic anemia continued to show a faster rate of leukocyte reconstitution to WBC 500 x 10(6)/l compared to patients with ANL, ALL or CML, and a faster rate to WBC 1000 x 10(6)/l than patients with CML.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of the pattern of interstitial pneumonitis following allogeneic bone marrow transplantation before and after the introduction of prophylactic ganciclovir therapy in 1989.

A comparison was made of the pattern of interstitial pneumonitis (IP) following allogeneic bone marrow transplantation before and after the introduction of ganciclovir prophylaxis to minimize the risk of cytomegalovirus (CMV) disease in the St Vincent's Hospital bone marrow transplant program in 1989. A total of 456 recipients of allogeneic transplants were included. 280 received no prophylactic ganciclovir while 176 received prophylactic ganciclovir. The overall incidence of interstitial pneumonitis dropped from 19.6 to 12.5% (P = 0.03) and this was primarily due to a reduction in the incidence of CMV-IP which fell from 12.9 to 1.7% (P < 0.0005). The incidence of idiopathic IP was not different between the two groups (6.3 vs 3.2%), nor was the incidence of Pneumocystis carinii pneumonia (2.9 and 0.6%). Prophylactic ganciclovir has thus had a significant impact in reducing both the overall incidence of IP and specifically cytomegalovirus IP in allogeneic marrow transplant recipients. The most common form of IP in patients given prophylactic ganciclovir is now idiopathic interstitial pneumonitis.

Preparative regimens for marrow transplantation containing busulphan are associated with haemorrhagic cystitis and hepatic veno-occlusive disease but a short duration of leucopenia and little oro-pharyngeal mucositis.

One-hundred-and-forty-three patients with haematological malignancy or severe aplastic anaemia received HLA-identical sibling bone marrow transplants. In 111 of these patients who had haematological malignancy and who were prepared for transplant with cyclophosphamide 120 mg/kg and fractionated total body irradiation 12-14 Gy, the incidence of haemorrhagic cystitis and hepatic veno-occlusive disease was 13% and 3%, respectively. In contrast, the incidence in 15 leukaemic patients prepared for transplant with chemotherapy regimens containing high-dose busulphan was 47% and 20%, respectively (p less than 0.001). Two patients in this latter group who developed fatal veno-occlusive disease had chronic myeloid leukaemia and had received long-term low-dose busulphan pre-transplant. Neither complication occurred in 26 patients prepared by cyclophosphamide alone (20 patients with severe aplastic anaemia) or with cyclophosphamide and melphalan (six patients with leukaemia). The regimen of busulphan 16 mg/kg in combination with cyclophosphamide 120 mg/kg was associated with a short duration of total leucopenia with a significantly higher leucocyte count on the day of marrow transplant compared to other regimens. Furthermore, oro-pharyngeal mucositis was not severe even when methotrexate was utilised as post-transplant prophylaxis for graft-versus-host disease. Thus, while the busulphan-cyclophosphamide regimen appeared useful, we suggest that (1) high-dose busulphan should not be used as a preparative regimen for patients previously exposed to busulphan, and (2) bladder irrigation (as well as intravenous hydration) is necessary to minimise haemorrhagic cystitis in patients given regimens that incorporate high-dose busulphan.

Prospective randomised double-blind trial of the in vivo use of recombinant human erythropoietin in bone marrow transplantation from HLA-identical sibling donors. The Australian Bone Marrow Transplant Study Group.

Ninety one patients between the ages of 17 and 58 years undergoing histocompatible allogeneic transplants from sibling donors were entered into a double-blind randomised trial to evaluate the effect of human erythropoietin (rhu EPO) at a dose of 300 units per kg/day given thrice weekly by intravenous injection on erythropoiesis and on erythrocyte and platelet transfusion requirements. Dose was ceased when the haemoglobin exceeded 12g/dL and recommenced if the haemoglobin fell below 12 g/dL, at 150 units/kg/day. If the haemoglobin exceeded 12 g/dL on a further occasion, the dose of rhu EPO was not given. Patients received two units of erythrocytes when the haemoglobin dropped below 8.5g/dL and received platelet transfusions when the count dropped below 20 x 10(9)/L. Univariate analysis revealed a significantly higher reticulocyte count, haemoglobin concentration and bone marrow erythropoiesis after day 14 in the group receiving rhu EPO but this was not reflected in decreased erythrocyte transfusion (7 +/- 5 in controls versus 6 +/- 5 in rhu EPO group) or in platelet transfusions (11 +/- 7 in controls versus 11 +/- 9 in rhu EPO group). Hospitalisation in each group was the same (29 +/- 8 in the control group and 28 +/- 8 in the rhu EPO group). However, in the multivariate analysis, the administration of rhu EPO was associated with an 18% reduction in erythrocyte transfusion requirement when other variables were taken into account. No side-effects due to rhu EPO were detected in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-malignant bone marrow necrosis: a report of two cases.

We present two cases of bone marrow necrosis not associated with malignancy, infection or sickle cell disease. The first case, a 28 year old woman with the antiphospholipid syndrome and a factor V Leiden abnormality, suffered an illness characterised by multiple organ thromboses, anemia and refractory thrombocytopenia. She had documented bone marrow necrosis of the posterior iliac spine and numerous hot spots on bone scanning suggestive of widespread marrow necrosis. This patient also suffered hepatic infarcts and a miscarriage and may represent an explanation for the previously described "catastrophic antiphospholipid syndrome". The second patient developed widespread bone pain over a three week period, underwent a cholecystectomy and suffered major post-operative complications including a delayed transfusion reaction and disseminated intravascular coagulation. Pancytopenia developed and bone marrow trephines from numerous foci revealed widespread bone marrow necrosis. The only predisposing factor to account for this presentation was that the patient had been sniffing glue for two months prior to the illness, as the foci of necrosis had healed on repeat marrow examination eight weeks later when the patient had abstained from glue sniffing. This case may represent a reversible, toxic cause of bone marrow necrosis.

Peripheral blood and bone marrow findings in patients with acquired immune deficiency syndrome.

In 4 years (1984-1987), 183 bone marrow examinations were performed on 155 human immunodeficiency virus (HIV) antibody positive patients. One hundred and fifty three had category IV AIDS. One-third of the marrows yielded specific information. This included opportunistic infection, in particular Mycobacterium Avium Intracellulare Complex (MAI) (24%), malignancy (4%), consistent with ITP (9%) and iron deficiency (1%). In the remaining two thirds of the bone marrows the most frequent non-specific abnormalities were dyserythropoiesis, erythroid hypoplasia, reticuloendothelial iron block, granulomas, lymphoid aggregates, plasmacytosis and histiocytosis. Common peripheral blood findings were anemia, lymphopenia, anisocytosis, rouleaux and atypical lymphocytes. Peripheral blood and bone marrow examinations on 16 patients on AZT are included. These patients have more pronounced blood and bone marrow abnormalities. The causes of these abnormalities are multifactorial and include low T4 levels, severe viral and other infections and therapy with marrow toxic drugs.

Metabolic abnormalities in adult acute lymphoblastic leukaemia (Burkitt cell type): case report.

A case is described of a 19-year-old male with acute lymphoblastic leukaemia (Burkitt cell type) who developed marked hypocalcaemia, hyperphosphataemia and acute oliguric renal failure from urate nephropathy following the initiation of chemotherapy.