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263 patients (median age 65+/-10 years) with multiple myeloma were treated with cyclophosphamide-prednisone. Out of this cohort, 103 patients had progressive disease and were randomly assigned to either VAD (vincristine, doxorubicin, dexamethasone; 50 cases) or VMBCP (vincristine, BCNU, cyclophosphamide, melphalan and prednisone; 53 cases). There were no statistical differences between the two groups with the respect to clinical, biological and radiological parameters. There was no difference in survival between the VAD and VMBCP groups. The 4 months response rate was similar in the two groups (50% VAD, 56% VMBCP). With multivariate analysis for survival (Cox model), two factors had a statistically significant impact: Karnofsky index (> 60) and albuminaemia (< 34 g/l). With both Karnofsky index > 60 and albuminaemia > or = 34 g/l, the median survival was 29 months v 2 months with a Karnofsky index < or = 60 and albuminaemia < 34 g/l (P<0.05). In conclusion, VAD or VMBCP had similar activity for salvage treatment in MM refractory or relapsing to first-line treatment with cyclophosphamide-prednisone.

Infection is a common adverse event after therapy with nucleoside analogs, including 2-chlorodeoxyadenosine (CdA). However, the incidence of CdA-related infections has been poorly documented. In this study we compare, in the same patient population, the incidence of infectious episodes during the 6-month period before CdA to their incidence during the 6 months after initiating therapy. Ninety-five patients with hematological malignancies were studied. The incidence of infectious episodes almost doubled after CdA (0.87 vs. 0.47 during the pre-CdA period). The following factors were associated with an increased risk of infection after therapy: a history of previous chemotherapy, infection during the pre-CdA period and a diagnosis of chronic lymphocytic leukemia or of non-Hodgkin's lymphoma. Age, neutrophil and lymphocyte count at onset of CdA and time interval between diagnosis and therapy with CdA did not correlate with the infectious risk. The pattern of infections was modified after therapy with an increase of herpes virus infections ( 1 vs. 8 episodes, p=0.04) and of fever of unknown origin (6 vs. 17 episodes, p=0.03). In conclusion, a population at high risk for developing infectious complications after CdA therapy can be identified. Specific measures aimed at reducing the incidence of infectious events should concentrate on this population.

Purpose: To study the prognostic significance of the small non-cleaved-cell lymphoma (SNCCL) histologic subtype, we compared the outcome of adult patients with SNCCL with that of patients with aggressive lymphoma other than SNCCL by means of two case-controlled studies., Patients and Methods: We analyzed the results of the doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) regimen used as a reference scheme in our cooperative study group (Groupe d'Etude des Lymphomes de l'Adult [GELA]) in 52 adult SNCCL patients with no bone marrow (BM) or CNS involvement. Forty-five SNCCL patients younger than 60 years could be compared with two separate case-matched groups of patients with aggressive lymphoma other than SNCCL undergoing the same therapeutic regimen. In the first case-controlled study, matching ensured identity of each risk factor of the age-adjusted International Index (ie, Ann Arbor stage, performance status, and lactate dehydrogenase [LDH] level); in the second study, matching was performed according to the number of presenting risk factors (zero, one, two, or three), regardless of their nature., Results: The 5-year overall survival rates were not significantly different between SNCCL and control patients in both case-controlled studies: 48% versus 51% in the first study, and 48% versus 55% in the second study., Conclusion: These results support the thesis that in patients with no bone marrow or CNS involvement, the SNCCL histologic subtype does not confer a prognosis worse than that of other aggressive lymphoma.

To evaluate the prognostic value of the karyotype in acute myeloblastic leukemia when patients are allocated to have either autologous bone marrow transplantation (BMT) or allogeneic BMT at the time of first remission (CR1), we have prospectively followed 134 consecutive patients from diagnosis. CR was achieved in 118 patients. Allogeneic BMT and autologous BMT were performed in 25 and 43 CR1 patients, respectively. Applying the karyotype classification of Keating et al for remission duration (favorable: t(15;17), inv(16); intermediate: normal, X -Y, t(8;21); unfavorable: other abnormalities), 10 patients had a favorable, 49 an intermediate, and 44 an unfavorable karyotype. The 5-year leukemia-free survival (LFS) probabilities for patients with a good, intermediate and unfavorable karyotype were 65%, 32% and 11%, respectively (log rank test P = 0.0019). The probabilities of relapse were 35% in patients with a favorable karyotype, 52% with an intermediate karyotype and 87% with an unfavorable karyotype (P = 0.0004). In the patients who had autologous BMT in CR1, the LFSs were 100%, 33% and 10% with favorable, intermediate and unfavorable karyotype, respectively (P = 0.04). The karyotype was of no prognostic value in patients receiving allogeneic BMT who had BMT in CR1. This study shows that the karyotype retains its prognostic value when the intentions is to treat patients with acute myeloblastic leukemia in CR1 with BMT. Autologous BMT was not able to improve the poor prognosis associated with an unfavorable karyotype.

The nucleoside analog 2-chlorodeoxyadenosine (2-CdA) has recently emerged as a most promising treatment for hair-cell leukemia (HCL). The response rates are high regardless of prior therapy, and the duration of complete responses (CR) after a single course of treatment is longer than with any other therapeutic agent. We investigated the presence of minimal residual disease (MRD) in ten HCL patients treated in our institution with 2-CdA. The presence of residual leukemic cells was investigated in patients in CR following one course of treatment, using the polymerase chain reaction (PCR) and heavy-chain immunoglobulin genes (IgH), or TCR delta derived clonospecific probes. Eight patients achieved a complete remission after a single course of treatment, as evaluated at 6 months. Among these patients, seven are still in CR with a median follow-up of 12 months (range, 6-20 months) and one has relapsed after 15 months. Using PCR, all the evaluable patients remaining in CR showed persistent evidence of detectable MRD with no sign of decrease over the observation period. From this small series, we conclude that a single course of 2-CdA does not eradicate HCL and that persistence of residual leukemic cells appears to be common in patients in complete morphologic remission. Whether persistence of MRD will have an impact on long-term outcome, or whether HCL patients in morphologic CR with persistent MRD will remain so, is a matter of longer follow-up.

The response of human pancreatic polypeptide (hPP) to a protein-rich meal was investigated in 4 groups of subjects: 1) normal controls (n = 11); 2) patients with recent onset type I diabetes, showing no sign of cardiovascular autonomic neuropathy (CAN) (n = 9); 3 and 4) patients with long standing type I diabetes without and with overt CAN (n = 12 and 10 respectively). Patients belonging the group 3 and 4 had equivalent duration of diabetes (17 and 20 years respectively). The mean integrated early hPP responses (0-30 minutes) were respectively (ng. min. ml-1; mean with range): 1) 9.4 (3.3-24.2); 2) 7.4 (0.7-22); 3) 4.8 (0-14.2); 4) 5.4 (0-14.9). The integrated total responses (0-120 minutes) were respectively: 1) 44.0 (12.7-98.7); 2) 39.0 (11.6-118.1); 3) 29.8 (0-81.2); 4) 25.9 (0-71.6). In the group with long standing diabetes, the early and total integrated hPP responses of the patients with CAN did not differ significantly from those without CAN. Early hPP responses of patients with long standing diabetes (group 3 and 4) were slightly (P less than 0.05) lower than those of controls. 5 patients with long standing diabetes had no detectable post-prandial hPP rise, a feature never observed in normals or recent onset diabetics. Two of these had no sign of CAN. These data suggest that an absence of hPP response to a mixed meal may be one of the expression of digestive autonomic neuropathy in long standing diabetes and that impaired hPP response may sometimes be dissociated from overt CAN.

Internists are frequently faced with the problem of interpreting hormonal values and the results of endocrine tests in elderly patients. In this review, endocrine changes observed in the course of the ageing process are systematically examined for each endocrine gland. The causes of the modifications observed can for the sake of simplicity be classified into three types: 1. Reduction of the hormone's metabolism with, subsequent to its prolonged half-life, a reduction of secretion due to an appropriate feedback mechanism, without modification of the secretory capacity of the glands involved (e.g. thyroid hormones and cortisol). 2. Reduction of hormonal secretion as a consequence of loss of glandular mass (e.g. the gonads). 3. Changes in the sensitivity of target cells to a hormone (e.g. insulin, ADH, catecholamines, lactotrope cells, TRH and hypothalamus to steroids) due to either loss of receptors or modifications in post-receptor events.

The effect of chronic hyperestrogenism on gonadal function was studied in three men who had estrogen-secreting Leydig cell tumors before unilateral orchidectomy and for 11-43 months after surgery. All three men had low plasma gonadotropin and testosterone levels and increased estradiol levels. Impairment of testicular steroidogenesis was also suggested by increased progesterone to 17-hydroxyprogesterone and 17-hydroxyprogesterone to androstenedione ratios in both spermatic venous plasma and the medium of Leydig tumor cells from one patient incubated in vitro. Before surgery, spermatogenesis was abnormal in two men. Testicular endocrine function and spermatogenesis did not return to normal after surgery. During the follow-up period, plasma gonadotropin levels were high in all three men, and testosterone was low normal. Estradiol levels decreased to normal immediately after surgery and then returned to the upper normal limit. The response to hCG stimulation in one man was subnormal. We conclude that chronic hyperestrogenism produced hypothalamo-pituitary inhibition as well as direct steroidogenic blockade at the testicular level. Long term impairment of both endocrine and exocrine testicular functions may be secondary to slowly reversible (or irreversible) estrogen-induced damage to tubular and Leydig cells.

A 29-year-old patient developed a bronchoesophageal fistula after expectorating a mycetoma caused by Aspergillus fumigatus. After failure of medical therapy, a retrosternal coloplasty was performed. Pulmonary aspergillosis can be the cause of a bronchoesophageal fistula.