Anthony J. Dodds

Granulocyte colony-stimulating factor and neutrophil recovery after high-dose chemotherapy and autologous bone marrow transplantation.

Granulocyte colony-stimulating factor (G-CSF) was administered by continuous subcutaneous infusion to 15 patients with non-myeloid malignancies treated by high-dose chemotherapy and autologous bone marrow infusion. G-CSF was given at variable dosage based on neutrophil count. Sustained serum levels of G-CSF were achieved. Neutrophil recovery was accelerated in G-CSF treated patients compared with 18 historical controls and exceeded 0.5 x 10(9)/l at a mean of 11 days after marrow infusion compared with 20 days for controls, a significant difference. This reduction led to significantly fewer days of parenteral antibiotic therapy, 11 versus 18 days in controls, and less isolation in reverse-barrier nursing, 10 versus 18 days.

Cyclosporin A associated nephrotoxicity in the first 100 days after allogeneic bone marrow transplantation: three distinct syndromes.

Summary. Thirty‐six patients received allogeneic (34) or syngeneic (two) bone marrow transplants as treatment for severe aplastic anaemia or acute leukaemia. Nineteen of the allogeneic recipients received methotrexate (MTX) and 15 received cyclosporin A (CyA) as the predominant immunosuppressive agent to minimize graft‐versus‐host disease (GVHD) post transplant. In the first 100 d post transplant renal dysfunction was much less frequent in the MTX recipients than in the CyA recipients who exhibited three distinct syndromes of nephrotoxicity: most commonly, CyA recipients developed asymptomatic azotaemia, proteinuria, urinary casts, impaired urinary concentrating ability and hypertension. Secondly, two CyA recipients developed acute reversible renal failure precipitated by systemic bacterial infection which required dialysis and in which the kidney was the sole target organ; thirdly, two recipients of HLA‐genotypically non‐identical grafts developed a rapidly progressive fatal syndrome with multiple organ involvement including lung, brain and kidney which clinically and histologically resembled thrombotic thrombocytopenic purpura.

Cyclosporine-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.

The toxicity of busulphan and cyclophosphamide as the preparative regimen for bone marrow transplantation

Summary. The toxicity of the conditioning regimen of high dose busulphan (Bu) (16 mg/kg) and cyclophosphamide (Cy) (120 mg/kg) has been compared to cyclophosphamide (Cy) (120 mg/kg) and fractionated total body irradiation (TBI) 12‐14 Gy. Since 1985, 67 patients have received conditioning of Bu and Cy for HLA‐identical sibling bone marrow transplants. 166 patients have received Cy and TBI since 1981.

Tranexamic acid and upper gastrointestinal haemorrhage--a double-blind trial.

The efficacy of antifibrinolytic therapy in the management of acute upper gastrointestinal haemorrhage has been investigated in a double-blind clinical trial. Two-hundred patients were studied using tranexamic acid, a potent antifibrinolytic agent. Of these, 103 were in the treatment group and 97 in the control group. Patients were analysed to determine severity of initial blood loss, transfusion requirements, together with the incidence of recurrent bleeding, surgical intervention, and death. Final diagnosis as to the site of bleeding was arrived at using endoscopy, barium studies, and the findings at operation and necropsy. The groups were well matched as regards severity of initial haemorrhage, age, sex, aetiological diagnosis, and precipitating factors. A significant difference was observed in the requirement for surgical intervention to control continuing or recurrent haemorrhage. Twenty-three of 97 in the control group and seven of 103 in the treatment group required surgery.There appeared to be a reduction in the transfusion rate after the first three days of hospitalization in the treatment group. There were no significant differences in mortality or in side-effects between the two groups.

Prophylactic use of ganciclovir in allogeneic bone marrow transplantation: absence of clinical cytomegalovirus infection

Ganciclovir was given prophylactically to 25 patients receiving allogeneic bone marrow transplants for haematological malignancy. Patients who were seropositive for cytomegalovirus (CMV) pre‐transplant were given ganciclovir both pre‐ and post‐transplant. Those who were CMV seronegative, but who received marrow from a CMV seropositive donor, received ganciclovir post‐transplant. No non‐haemopoietic toxicity was observed. Toxicity was restricted to late reversible haematological toxicity in four of the 19 evaluable patients (one thrombocytopenia, one pancytopenia, two leucopenia). No CMV interstitial pneumonitis (IP) was observed, nor were any other clinically manifest CMV infections detected. Sixteen patients remain alive at > 84 to > 518 d post‐transplant. In a retrospective comparison of 152 recipients of allogeneic transplants for haematological malignancy not given prophylactic ganciclovir, and in whom either the recipient or the donor or both were CMV seropositive, the incidence of all clinically manifest CMV infections was 23% (P= 0·02) and that of CMV IP 17% (P= 0·05). If only patients in the study group and the control group receiving the same cyclosporin/short methotrexate prophylactic immune suppressive regimen, the same prophylactic acyclovir regimen and the same CMV and leucocyte‐filtered blood product transfusion strategy were considered, the incidence of all clinically manifest CMV infections in the control group was 24% (P= 0·01) and that of CMV IP 13% (P= 0·07). Ganciclovir appears to reduce the incidence of CMV infections in allogeneic marrow transplant recipients even in those given immune suppressive regimens associated with adequate control of acute graft‐versus‐host disease.

Factors affecting the outcome of allogeneic bone marrow transplantation for adult patients with refractory or relapsed acute leukaemia

We evaluated the outcome of allogeneic bone marrow transplantation (BMT) for advanced acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) in 383 adult patients in nine Australian adult BMT centres between 1981 and 1997. The median overall survival for the group was 4.8 months, with an estimated 5‐year survival of 18%. 28% of patients died of transplant‐related toxicities within the first 100 d. Progressive disease was responsible for 48% of deaths. Multi‐factor analysis demonstrated that AML (v ALL), disease status (second complete remission [CR2] v others), age (< 40 years) and duration of prior first complete remission (CR1) (> 6 months) were pre‐transplant variables significantly associated with improved survival. Acute graft‐versus‐host disease (GVHD) of any grade reduced the rate of relapse in both AML and ALL, but only grades I–II were associated with improved survival. Both limited and extensive chronic GVHD were associated with increased survival. Only patients with AML in untreated first relapse or CR2, with a duration of CR1 > 6 months, or patients with T ALL, had a 5‐year survival > 20%. Transplants for AML in induction failure or pre‐B ALL in untreated first relapse or CR2 had an intermediate outcome, with 5‐year survival of 10–20%. A 5‐year survival of < 10% was observed for patients transplanted for ALL in induction failure or for pre‐B ALL or AML in refractory first relapse or beyond CR2. These results suggest that for most adult patients with advanced acute leukaemia an allograft offers only a small chance of cure.

Haemorrheological response to plasma exchange in Raynaud's syndrome.

Eight patients with Raynauds syndrome were treated by weekly plasma exchange for four weeks using a Haemonetics Model 30 Blood Processor. The mean whole-blood viscosity at a shear rate of 0.77/s was significantly lower after treatment, and the mean index of red-cell deformability was significantly improved. In four patients studied serially the mean percentage fall in whole-blood viscosity after a single plasma exchange was 49% at 0.77/s but only 14% at 91/s. All patients noticed symptomatic improvement including healing of ischaemic digital ulcers. In six patients the number of digital arterial segments containing detectable blood flow was measured by directional Doppler; in all six the number increased. It is concluded that plasma exchange is an effective means of haemorrheological treatment and may be beneficial in patients with digital ischaemia.

Oral administration of cyclosporin A for recipients of allogeneic marrow transplants: implications of clinical gut dysfunction

Summary. Cyclosporin A (CyA) was used to minimize graft‐versus‐host disease (GVHD) in 28 recipients of allogeneic marrow transplants. When given orally, the absorption of CyA was markedly dependent on normal gut function. Patients without gut dysfunction showed normal serum concentration‐time curves while those with diarrhoea from any cause (chemo‐radiation enteritis, acute GVHD of the gut, infectious enteritis) showed minimal absorption of the drug. These data indicate the desirability of the intravenous administration of CyA during periods of gut dysfunction in marrow transplant recipients.

Serum erythropoietin changes in autologous and allogeneic bone marrow transplant patients

Summary. Sequential changes in serum erythropoietin (sEPO) levels were measured by radioimmunoassay in six patients receiving autologous rescue (AR) and 11 patients receiving an allogeneic bone marrow transplant (BMT) for malignant disease.