J. Bury

Simultaneous assays of cancer-associated antigens in various neoplastic disorders.

Five tumor markers were measured simultaneously in serum by radioimmunoassay: carcinoembryonic antigen (CEA), alpha‐fetoprotein (AFP), human chorionic gonadotropin (HCG), the β subunit of HCG, and Kappa casein. In a population of 935 normal subjects these antigens were undetectable or found within precise limits. In patients with tumors of various origins the rate of pathologically elevated levels was 72% at the beginning of the clinical course (194 cases). This high rate was primarily due to the simultaneous measurement of CEA, βHCG, and casein. AFP was of little importance. The simultaneous measurement of these tumor markers may be one biochemical element of diagnosis of carcinoma, although this criterion is neither absolute nor specific, as 14.7% of patients with non‐neoplastic disorders (234 cases) were positive for one antigen. In the presence of metastases (112 cases) the rate of pathologic levels of at least one antigen was increased: 86% due to CEA and casein assay at the same time as their absolute levels were increased. Surgical removal reduces the rate of positivity of these antigens to 37%. As was shown in patients with breast cancer, the rate was 10% when the tumor had been removed at Stage N− and 54% when it was removed at Stage N+. Thus, the persistence of pathologic levels could be correlated with the capacity for recurrence or metastases. Finally chemotherapy, radiotherapy, or both, do not decrease the rate of positivity of the tumor markers.

Treatment of acute nonlymphocytic leukemia in young and elderly patients.

Among 95 consecutive patients with acute nonlymphocytic leukemia (ANLL), 61 were treated with a high‐dose chemotherapeutic induction regimen consisting of daunorubicin, vincristine, and cytosine arabinoside (DOA). The complete remission (CR) rate was 66%. Although young patients responded better than older patients, only sex was found to be of prognostic significance for achieving CR (84% CR in men versus 47% in women, P < 0.005, independent of age). Patients in CR received consolidation, monthly maintenance therapy, and late intensification for a period of 2 years. Median remission duration was 57 weeks and median survival, 93 weeks. Projected CR rate at 5 years was 30%. CR and survival duration were significantly longer in patients 40 to 60 years old when compared with younger and older patients (P = 0.023). They were also longer in male than in female patients (P = 0.018), but this may be due to an effect of age. In the 34 patients who did not receive DOA treatment because of age or poor clinical conditions, there was no survival beyond 57 weeks, except in a 73‐year‐old woman who reached a spontaneous remission during acute infection. ANLL characteristics at presentation revealed a tendency toward a smaller tumor mass (P < 0.05) and rarer Auer rods present (P = 0.03) with increasing age. Features and treatment of ANLL in elderly patients are discussed in view of the poor results obtained with conservative management.

Observations of serum trace elements in chronic lymphocytic leukemia.

Serum trace elements (STE) were measured in 50 patients with chronic lymphocytic leukemia (CLL) and 100 normal subjects. Copper was higher in patients than in controls (1.50 ± 0.06 versus 1.10 ± 0.02 μg/ml, P < 0.001), increased steadily from Stage 0 to Stage 4 (P = 0.002), and correlated with the lymphocyte count and serum lactate dehydrogenase (P < 0.01) but not with acute phase reactants. Zinc was lower in patients than in controls (0.94 ± 0.03 versus 1.10 ± 0.02 μg/ml, P < 0.001). Zinc (NS), selenium (P = 0.039), and calcium (P < 0.033), were decreased in Stages 3–4 as compared to Stages 0–2. The copper‐to‐zinc ratio (CZR) increased continuously from Stage 0 to Stage 4 (P < 0.001). Discriminant analysis between two groups, Stage 0–2 and Stage 3–4, based on serum copper, zinc, calcium, and protein levels, allowed for a correct classification of 94% of the patients. Moreover, the clinical staging of the remaining 6% was modified retrospectively according to the results of discriminant analysis. It was concluded that (1) serum copper and CZR are useful indices of the extent of disease, (2) they are independent of a nonspecific acute phase reaction, (3) STE determination could be helpful in the staging of a limited number of CLL patients, and (4) zinc deficiency could contribute to immune dysfunction in CLL.

Long term follow-up of patients with acute myelogenous leukemia who received the daunorubicin, vincristine, and cytosine arabinoside regimen.

In 1985, the authors published a study of acute myelogenous leukemia (AML) patients treated with a chemotherapeutic regimen that was then considered intensive. Ten years later, the authors reanalyzed the same cohort to determine whether the very promising actuarial results observed at 5 years held after longer follow‐up.

Serum zinc and copper as prognostic factors in acute nonlymphocytic leukemia.

A total of 44 patients were treated with intensive induction chemotherapy for acute nonlymphocytic leukemia (ANLL). A complete remission (CR) was obtained in 29/44 (66%) patients. Serum zinc (Zn) and copper (Cu) were studied as possible prognostic factors in the determination of the chance of a patient attaining remission. Pretreatment Zn was higher in patients attaining a remission (0.99 +/- 0.05 microgram/ml) than in patients failing to attain a CR (0.78 +/- 0.06 microgram/ml) (P = 0.0216). There was no further difference between the two groups during aplasia. However, when response to treatment was evaluated about day 28, the difference reappeared: 1.06 +/- 0.05 microgram/ml for CR patients vs 0.77 +/- 0.07 microgram/ml for failures (p = 0.0012). Pretreatment Cu was higher in responding (1.44 +/- 0.07 microgram/ml) than in nonresponding (1.06 +/- 0.05 microgram/ml) patients (p = 0.0002). The difference between the two groups remained highly significant at days 7, 14, 21, and 28. At the time of response evaluation, the values were 1.46 +/- 0.05 microgram/ml for CR patients vs 1.19 +/- 0.08 microgram/ml for non-CR patients (P = 0.0070). We conclude that the measurement of serum Zn and Cu may be helpful in the prediction of response to chemotherapy in patients treated for ANLL.

Donor lymphocyte infusion for late relapse followed by kidney transplantation for end-stage renal failure after allogeneic bone marrow transplantation for chronic myeloid leukemia

A 36-year-old man was diagnosed in 1986 with chronic phase (CP) chronic myeloid leukemia (CML). Three months later, he developed a blast crisis and blastic embolization of his left tibial artery requiring a left foot amputation. After successful induction and consolidation therapy, the patient (then in second CP) underwent an allogeneic bone marrow transplantation (BMT) from his human leukocyte antigen-identical brother. The conditioning regimen consisted of cyclophosphamide, cytarabine, and 8-Gy total body irradiation, and graft-versus-host disease (GVHD) prophylaxis was carried out with cyclosporine A alone. The immediate posttransplant course was complicated by grade 3 GVHD that was successfully treated with steroids and methotrexate, and the patient was discharged on day 43. At that time, his serum creatinine was 16 mg/L (Fig. 1). Limited chronic GVHD was diagnosed on day 100 and was successfully treated with psoralen and long-wave ultraviolet radiation. Thereafter, the evolution remained uneventful except for hypertension. Although cyclosporine A was discontinued on day 420, his renal function progressively degraded (Fig. 1). In 1994, the patient’s serum creatinine was 32 mg/L and a renal biopsy revealed tubulointerstitial nephritis with nephrosclerosis. Gradual deterioration of his renal function resulted in the institution of maintenance hemodialysis in August 1996. A kidney transplant from his marrow donor brother was considered in March 1998. However, the patient’s bone marrow analysis at that time showed a cytogenetic relapse (4 of 26 phi-positive metaphases) and mixed chimerism. He thus received donor lymphocyte infusion (DLI) (1 10 CD3 cells/kg). The patient did not experience acute or chronic GVHD, and bone marrow analyses 3 and 7 months later showed a complete cytogenetic and molecular response. Chimerism analysis in December 1999 demonstrated full donor chimerism. After his brother, who had given bone marrow to him 14 years earlier, was found to be an acceptable donor, kidney transplantation was performed in April 2000, without any immunosuppressive therapy. The transplanted kidney functioned immediately, and a kidney biopsy performed 6 months after the transplant did not show any sign of graft rejection (Fig. 1). Now, more than 2 years after kidney transplantation, the patient is well with normal renal function and without any sign of GVHD or CML. Although late-onset renal failure occurs in up to 20% of survivors of allogeneic bone marrow transplantation, chronic renal failure requiring dialysis is a relatively rare event in the BMT setting (approximately 2% of the patients) (1). The feasibility of kidney transplantation after allogeneic BMT has already been reported (2–4). However, our report is unique in that the patient was in relapse when the kidney transplant procedure was contemplated but could be rescued by a DLI. It is now well established that DLI can cure CML in patients relapsing after an allogeneic transplant (5). Because leukemic relapse may be accompanied by residual host hematopoiesis that would imply a requirement for restoration of immunosuppressive therapy to avoid kidney graft rejection and thereby alter the DLI-mediated graft-versus-leukemia effect, we decided to delay kidney transplantation until well after DLI and achievement of full donor chimerism. In conclusion, our report emphasizes that renal transplantation should not be ruled out in patients with DLI-sensitive disease relapsing after an allogeneic BMT.

Une Complication Rare Du Zona Ophtalmique: L’Arterite Cerebrale De Propagation

SummaryWe are reporting the case of a 55-year-old man with stage II chronic lymphoid leukemia, complicated by Herpes zoster ophtalmicus with contralateral hemiplegia. This hemiplegia has been interpreted as the consequence of a granulomatous angiitis. Anti-viral drugs should be useful in the treatment of these cases.

P1 incompatibility in pigeon breeders.

Pigeon breeders of the P2 blood phenotype may develop anti‐P1 haemagglutinins as a consequence of natural immunization to pigeon dust. The half‐life of labelled P1 erythrocytes was determined in two P2 pigeon breeders otherwise compatible except for the presence of anti‐P1 antibodies and in four compatible controls without anti‐P1. The half‐life of tagged cells was within the normal range in one breeder but significantly reduced in the other, indicating that P1 incompatibility may occur in vivo. Since anti‐P1 antibodies are found in about 20% of P2 pigeon breeders, it is suggested that this group may be prone to developing an incompatibility to transfused P1 red cells.