Norman P. Lucie

The Prognostic Significance of the CD34 Antigen in Acute Myeloid Leukaemia

The prognostic value of CD34 expression on leukaemic blast cells was assessed in 38 patients with acute myeloid leukaemia. Nineteen patients had more than 10% CD34 positive blast cells. Median survival for the CD34 positive patients was 125 days and for the CD34 negative patients the median survival has not yet been reached at day 575 (p = 0.06). Of those patients who received intensive chemotherapy, CD34 positive patients (n = 13) had a median survival of 150 days while for CD34 negative patients (n = 14) the median survival has not yet been reached (p = 0.01). Adjustment for age and pre-existing myelodysplastic syndrome did not affect the correlation of CD34 positivity with survival (p = 0.02). Over the period of observation (median 10 months, range 2-19 months) the relative risk of death was 5 times greater for the CD34 positive patients. This study suggests that CD34 expression is an adverse prognostic marker, independent of age and pre-existing myelodysplasia.

High-dose cyclophosphamide and VP 16 as late dosage intensification therapy for small cell carcinoma of lung.

SummaryThis study investigated the use of late dose intensification therapy (LDIT) with cyclophosphamide (180 mg/kg) and VP 16 (1 g/m2) plus autologous bone marrow rescue in 22 patients with small cell lung cancer (SCLC). These patients were selected from a group of 95 patients who received three courses of a five-drug induction regimen comprising cyclophosphamide (750–1000 mg/m2), adriamycin (40 mg/m2), VP 16 (100 mg/m2) for 3 days, methotrexate (50 mg/m2) and vincristine (2 mg) (CAVMO). There were 16 patients with limited disease, 8 of whom were in complete remission (CR) and 8 in partial remission (PR) after the induction therapy. The other 6 patients had extensive disease; 3 of these achieved CR and 3 PR after induction therapy. Of the 11 patients in PR, 5 responded to LDIT; 3 had a further PR, and 2 CR. Subsequent to LDIT radiotherapy 4000 cGy was given to the primary site in 10 of the 22 patients. Since the start of the study, 19 of the 22 patients have relapsed and died (median survival 11 months), while 3 remain alive and in remission at 11, 11, and 24 moths. Comparison of the survival of patients receiving LDIT with that of an equivalent group (with respect to staging and response to induction chemotherapy) of patients who received induction chemotherapy alone showed no significant difference. In this study, LDIT following conventional induction therapy in patients with chemosensitive tumours did not improve survival.

Prevalence and haemopoietic effects of low serum vitamin B12 levels in geriatric medical patients.

The clinical significance of low serum vitamin B12 levels in elderly people is controversial. We aimed to document the prevalence of a low serum vitamin B12 (< 175 pmol/l) in patients referred to a geriatric medical unit, and to determine whether haemopoiesis is commonly affected in elderly patients with low serum vitamin B12. We studied prospectively 472 consecutive referrals to a geriatric medical unit; fifty-six (13%) had a low serum vitamin B12 level, of whom nineteen (34%) of the fifty-six also had evidence of Fe deficiency (serum ferritin < 45 ng/ml). Low vitamin B12 was associated with a raised mean erythrocyte volume (MCV; mean 96.0 (SD 6.7) fl), compared with a control group (91.7 (SD 6.0) fl; P = 0.001). However, only thirteen (23%) of the fifty-six patients with a low vitamin B12 had an MCV > or = 100 fl. Mean haemoglobin (Hb) levels were not significantly reduced in those with a low vitamin B12. In a subsequent study the haematological response to intramuscular hydroxocobalamin was examined in thirty-four patients with a low serum vitamin B12. Treatment resulted in a significant fall in MCV and rise in Hb; these effects could be detected both in those patients with an initially normal full blood count (change in MCV -1.2 (SD 1.2); Hb +0.5 (SD 0.6); P < 0.01) and in those with macrocytosis and/or anaemia (-9.1 (SD 11.8); +0.8 (SD 1.2); P < 0.05). A low serum vitamin B12 is common in geriatric medical patients. This is usually associated with an upset in erythropoiesis, although the abnormalities are often subtle and may not be apparent on inspection of the full blood count. Elderly patients with serum vitamin B12 < 175 pmol/l should be assumed to have vitamin deficiency even if their full blood count is normal.

Use of the Erythrogram in the Diagnosis of Iron Deficiency in Elderly Patients

In elderly patients the diagnosis of iron deficiency from full blood count indices is often difficult. We assessed an automated technique (numerical data of the erythrogram; Technicon H*1) by which the proportions of microcytic (< 60 fl) and/or hypochromic (< 28 g.dl-1) red blood cells are determined. Of 472 elderly patients investigated, 100 (21%) were found to have iron deficiency (plasma ferritin < or = 45 ng.ml-1). Less than two-thirds of patients with iron-deficient erythropoiesis (anaemia or microcytosis) had increased proportions of hypochromic and/or microcytic red blood cells. Furthermore, the erythrogram was not sensitive in detecting latent or early iron deficiency. The erythrogram also lacked specificity for iron deficiency anaemia as many patients with mild normocytic anaemia associated with chronic inflammatory disease had increased proportions of hypochromic and/or microcytic red blood cells. Although patients with iron deficiency had increased proportions of hypochromic normocytic (p < 0.01) and normochromic microcytic red blood cells (p < 0.05) compared to those with chronic inflammatory disease and normal or raised iron stores (ferritin > or = 100 ng.ml-1, n = 32), there was a large overlap between these two groups, and the grossly elevated erythrogram results in patients with iron deficiency were almost always associated with a mean cell volume (MCV) < 80 fl, whereas none of the patients with chronic inflammatory disease and normal or raised iron stores had an MCV < 80 fl. Thus the erythrogram does not appear to be of value in the routine assessment of iron status in elderly patients.

Meningeal relapse in Ph1-positive acute lymphoblastic and lymphoid blast crisis of chronic granulocytic leukemia. Is CNS-prophylaxis indicated?

Two cases of Ph1‐positive acute lymphoblastic leukemia (ALL) and one case of lymphoid blast crisis (LyBc) of chronic granulocytic leukemia (CGL) treated with standard chemotherapy for ALL are presented. Hematologic remissions lasting 6, 12, and 15 months were achieved in all cases. Meningeal relapse occurred in all three, terminating remission in two cases and occurring immediately after systemic relapse in the third. No CNS‐prophylaxis was given to the patient who relapsed at six months. Methotrexate (MTX) atone or combined with cranial irradiation formed the prophylaxis given in the other cases. Experience of these patients together with an analysis of reported cases of Ph1 ALL and CGL–LyBc suggests CNS‐prophylaxis may prolong first remission. A large scale trial of this appears indicated.

Radon and Acute Lymphoblastic Leukaemia

The incidence of Acute Lymphoblastic Leukaemia (A.L.L.) in an L.R.P. data collection survey has been compared with the indoor radon and gamma-ray exposure in 22 administrative counties in England and Wales. There is a strong correlation (r = 0.56, p < 0.01) for the incidence of childhood A.L.L. and indoor radon concentration. Weaker correlations were present in adults and no correlation with gamma-rays were obtained. A weak negative association of Hodgkins Disease with indoor gamma-rays was found. This data adds to the accumulating evidence suggesting an association between indoor radon and acute leukaemia.

Acute Cardiotoxicity After Daunorubicin in Acute Myeloid Leukaemia.

Use of the anthracycline antibiotics daunorubicin and adriamycin as antineoplastic agents is limited by dose-dependent, late cardiac toxicity. We describe a patient who developed fatal cardiogenic shock after comparatively low dose daunorubicin early in the treatment of acute myeloid leukaemia (A.M.L.). She was young with no previous cardiac history: investigations for an infectious aetiology were negative and at post-mortem there was no evidence of leukaemic infiltration. This unusual case demonstrates that standard doses of daunorubicin in A.M.L. may be followed early in the treatment by severe cardiac damage.