Myelopathy after intrathecal chemotherapy. A case report with unique magnetic resonance imaging changes.

BACKGROUND: Paraplegia caused by intrathecal chemotherapy has no known pathognomonic features and is a diagnosis of exclusion. METHODS: The authors reported the clinical and neuroimaging findings in one patient with this syndrome. RESULTS: The patient had severe paraplegia with urinary retention and impaired pain and touch sensation below T-10 with sparing of proprioception and vibration sense. Magnetic resonance imaging (MRI) scan showed diminished intensity throughout the central cervical spinal cord. Post-gadopentetate dimeglumine enhancement was scattered throughout the cervical spinal cord and in two areas of the dorsal spinal cord. Axial views of the cervical spinal cord showed that this enhancement was limited to the lateral columns. CONCLUSIONS: The MRI in myelopathy due to intrathecal chemotherapy may show a unique pattern of postgadopentetate dimeglumine enhancement limited to the lateral columns of the spinal cord. However, two recently encountered patients with the same syndrome did not show similar changes.

Double-blind randomized study of the effect of infusion rates on toxicity of amphotericin B.

Results of a double-blind randomized non-crossover study of rapid (45 min) versus slow (4 h) infusion of amphotericin B administered to 20 patients with proven or suspected fungal infection are reported. Toxicity was higher in the rapid infusion group than it was in the slow infusion group (mean total 7-day chill score, 173 +/- 276 versus 20 +/- 30 [P less than 0.01]; mean total 7-day dosage of meperidine required to abate rigors, 180 +/- 133 versus 58 +/- 78 mg [P less than 0.05]; and mean maximum total 7-day pulse rise, 225 +/- 64 versus 135 +/- 56 beats per min [P less than 0.02], respectively). When analyzed on a daily basis, the mean chill score, meperidine dosage, and pulse rise were also higher; and in addition, nausea and vomiting (5 of 11 patients who received a rapid infusion versus 0 of 9 patients who received a slow infusion [P less than 0.01]) appeared to be more common in those who received amphotericin B rapidly. The daily analysis approach proved that tolerance to these side effects developed with each subsequent infusion day, and by day 7 the incidence and severity were the same. This development of tolerance was significant for the mean chill score in the rapid infusion group (P less than 0.05) and for the proportion of patients with chills (P less than 0.005 for the slow infusion group; P less than 0.05 for the rapid infusion group). A decrease in creatinine clearance to greater than 51% of the baseline value was seen in two patients in each group. There were five deaths (four in the rapid infusion group, 1 in the slow infusion group) within 1 month, but none was clearly related to the amphotericin B infusion. The mean time to defervescence was similar for each group (10.8 +/- 4.1 days in the slow infusion group versus 9.9 +/- 5 days in the rapid infusion group). A rapid infusion regimen for amphotericin B cannot be recommended, at least during the first 5 to 7 days of treatment.

Multiple myeloma: A review of 92 cases at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

A review of 92 cases of multiple myeloma (66 males and 26 females) seen at the King Faisal Specialist Hospital and Research Centre from October 1975 through December 1987 revealed the age for affected patients ranged from 23 to 90 years (mean, 56 years). Six percent of the patients were less than 40 years old at the time of diagnosis. Bone pain was the most common presenting symptom in our patients (80%), most frequently involving the back. Anemia was the initial finding in 74%, followed by plasmacytoma (22.8%), hypecalcemia (19.6%), and renal insufficiency (18.5%). Skeletal survey abnormalities were seen in 92.4% of the cases, with osteolytic lesions as the predominant finding. Serum protein electrophoresis showed a monoclonal paraprotein in 78% of the cases, of which 55.5% were the IgG class. Free light chains were detected in the urine of 20 patients. The median survival time for all patients was 68 months. Twenty patients died of renal failure and/or infection. The combination of melphalan and prednison was used for treatment in 37 patients, while 31 patients received the M2 protocol and 19 patients received different therapy such as VCEP (vindesine, cyclophosphamide, VP 16 and prednisone), MPV (melphalan, prednisone, and vincristine) or high-dose melphalan. Five patients either refused treatment or died before treatment could be started.

Cytogenetics of acute promyelocytic leukaemia: incidence of t(15;17) at the Royal Marsden Hospital, London.

This is the first report from a laboratory in the U.K. of the incidence of t(15;17) in acute promyelocytic leukaemia. One of the cases has a variant translocation, t(15;17)(q22;q25). A t(15;17) translocation was present in all cases considered to be adequately studied.

Detection of micrometastases in patients with primary breast cancer.

An immunocytochemical method was used to screen smears obtained at primary surgery from multiple bone-marrow sites in 110 patients with breast cancer; at this time other techniques did not reveal metastases. Tumour cells were detected in the bone-marrow of 31 (28%) patients. The number of cells detected ranged from 1 to greater than 500; none was detected in conventionally stained smears. Patients in whom conventional criteria indicated a very poor prognosis seemed more likely to have such micrometastases. A further follow-up period is required to determine whether patients with micrometastases relapse earlier than those in whom no tumour cells are demonstrable.

Mismatched family donors for bone-marrow transplantation as treatment for acute leukaemia.

35 patients were treated for acute myeloid leukaemia or acute lymphoblastic leukaemia with allogeneic bone-marrow grafts from a parent, child, or sibling who was mismatched at the major histocompatibility complex (MHC). 11 of these patients are alive at least 6 months after grafting, 5 of them after more than 2 years. Of the 15 patients aged under 20 at the time of the graft, 8 are alive and well 6 months to 3 years later. Cyclosporin A was given to all patients after grafting. 1 patient died of acute graft-versus-host disease and in 2 other cases this was a major factor in their death. Graft failure caused the death of 2 patients. 4 patients died of recurrent leukaemia. A fatal complication in 12 patients was pulmonary oedema, often associated with convulsions, intravascular haemolysis, and renal failure. Some of these patients had viral or bacterial infections, but in the majority the syndrome was not associated with demonstrable infection. This syndrome, in which the essential lesion appears to be vascular, was much more common in recipients of mismatched than matched grafts. 3 others died from lung disease in which infection was a factor.

Mianserin and blood dyscrasias.

1 The haematological side-effects of mianserin have been studied. 2 There are 26 reported cases, of which 19 appear to show a definite association with the drug. A high proportion are female. 3 A reversible agranulocytosis has been most commonly observed, occurring between four and six weeks of treatment. On cessation of therapy, the counts have recovered. 4 Three patients have died, following a longer course of treatment. Two of these were septicaemic and the third, thrombocytopenic in addition. This is probably related to a failure of marrow recovery owing to the longer exposure, in the third case progressing to aplasia. 5 The number of reported dyscrasias is extremely small compared with the number of courses of mianserin prescribed. 6 It is desirable that a blood examination should be made at four weeks after starting treatment with mianserin to identify those patients at risk.

Ratio of blood and marrow-derived cells in bone marrow transplantation.

The content of the cell suspensions used in bone marrow transplantation can vary by at least twelvefold in the ratio of bone marrow-derived to blood-derived cells. The ratio is somewhat higher in young donors but is similar for male and female donors and is not closely correlated with the incidence of graft v host reactions.

Acute myeloid leukaemia: comparison of support required during initial induction of remission and marrow transplantation in first remission.

Two groups of patients with acute myeloid leukaemia (AML), treated concurrently, were compared to assess the support required during bone-marrow hypoplasia. One group of patients received drugs to induce initial remission; patients in the other group (in first remission) each received a bone-marrow transplant from a matched allogeneic sib. The patients who received marrow transplants required less time in hospital, were febrile on fewer days, received less therapeutic antibiotic treatment, and had fewer bacterial infections. They also required half as many units of platelets and blood per 100 days. The mean weight-loss per patient was the same in each group, and no patient required intravenous feeding. Transplantation for AML in first remission requires less supportive care than initial remission induction.

Increased detection of mammary carcinoma cells in marrow smears using antisera to epithelial membrane antigen.

We have developed a technique for the immunocytochemical staining of marrow smears using antiserum to epithelial membrane antigen (EMA). This membrane component is confined to, but widely distributed in, epithelial tissues and tumours derived from them, and is strongly expressed by infiltrating breast carcinoma cells. Marrow aspirates from patients with both early and metastatic breast cancer have been examined, and the results of immunocytochemical staining compared with conventional cytology and histology. Staining with antiserum to EMA enabled us to detect small numbers of carcinoma cells, and increased the yield of positive samples. Furthermore, using this technique, we found malignant cells in the marrow of patients with primary breast cancer with no other evidence of metastatic disease. Thus immunocytochemical staining for EMA may be of value in the detection of micrometastases in patients with primary breast carcinoma.

Toxicity and immunosuppressive activity of binary combinations of 2'-deoxycoformycin and 2'-deoxyadenosine.

Treatment of mice with 2'-deoxycoformycin (dCf) for 5 days produced inhibition of spleen and lymph node adenosine deaminase (E. C. 3.5.4.4) activity but no hematologic toxicity or weight loss. A 64-fold elevation of erythrocyte dATP was observed. However, if mice were injected with 2'-deoxyadenosine (AdR) in combination with dCf, weight loss, hematologic toxicity, and liver cell necrosis occurred. These mice had a severe blood coagulation defect and a 73-fold elevation of plasma alanine transaminase activity, plasma prealbumin became undetectable, and erythrocyte dATP levels were elevated 1500-fold. Death during treatment appeared to be from acute liver failure since bone marrow toxicity was only detected following termination of treatment. These effects were not seen in mice receiving adenosine in combination with dCf. dCf, either alone or in combination with AdR, inhibited the contact sensitization to oxazalone in mice. The inhibition was associated with signs of systemic toxicity which were more pronounced in the combination-treated groups. If dATP is the toxic metabolic accumulated in the malignant cells of patients treated with dCf, we propose that AdR supplementation of treatment should be considered with extreme caution since severe damage to normal tissues might result.

The place of bone-marrow transplantation in acute myelogenous leukaemia.

28 patients with acute myeloid leukaemia (AML) in first remission were maintained on chemotherapy, consisting of courses of cytosine arabinoside and daunorubicin, and immunotherapy with irradiated AML cells and BCG. The relapse rate and survival rate of these patients were compared with those of a simultaneously treated group of 22 patients in first remission who received sibling bone-marrow transplants after cyclophosphamide (60 mg/kg) given for 2 days and followed by a single dose of 1000 rads total body irradiation. Substantially fewer transplanted patients (4 out of 22) than chemo-immunotherapy patients (19 out of 28) relapsed (p less than 0.005) and 14 (64%) transplanted patients remain alive, well, and disease-free. Survival curves of the two groups of patients show that the transplanted patients never fared worse than the chemo-immunotherapy patients. We suggest that when possible young AML patients in remission should be offered transplantation as an alternative form of treatment.

Cytogenetic follow-up study of acute non-lymphocytic leukaemia.

A cytogenetic study was made at diagnosis in 68 patients with acute non-lymphocytic leukaemia. The median survival time of the group of patients was 47 weeks. Patients with totally abnormal karyotypes in the bone marrow had a median survival of 14 weeks, whereas for those with only chromosomally normal cells the median survival was 52 weeks, and 47 weeks for those with normal and abnormal cells. Survival was not influenced by the presence or absence of clonal abnormalities. A cytogenetic follow-up study was made on 41 of these patients. One of the three patients, still in first remission after 3 years, originally had an 8;21 translocation. In general, the abnormalities present at diagnosis disappeared during remission and there was no evidence that clones of abnormal cells were produced by treatment. The chromosomal findings in relapse were not necessarily the same as those seen at diagnosis and the abnormal karyotypes found were usually not clonal in type. A simple kinetic technique, in which the yield of mitoses after 2 and 24 h is compared, may be used as an adjunct to cytogenetic studies in predicting relapse.