A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811

The goal of this phase II multicenter clinical trial was to evaluate a new intensive chemotherapy program for adults with untreated acute lymphoblastic leukemia (ALL) and to examine prospectively the impact of clinical and biologic characteristics on the outcome. One hundred ninety-seven eligible and evaluable patients (16 to 80 years of age; median, 32 years of age) received cyclophosphamide, daunorubicin, vincristine, prednisone, and L-asparaginase; 167 patients (85%) achieved a complete remission (CR), 13 (7%) had refractory disease, and 17 (9%) died during induction. A higher CR rate was observed in younger patients (94% for those < 30 years old, 85% for those 30 to 59 years old, and 39% for those > or = 60 years old, P < .001) and in those who had a mediastinal mass (100%) or blasts with a T-cell immunophenotype. Eighty percent of B-lineage and 97% of T-cell ALL patients achieved a CR (P = .01). The coexpression of myeloid antigens did not affect the response rate or duration. Seventy percent of those with cytogenetic or molecular evidence of the Philadelphia (Ph) chromosome and 84% of those without such evidence achieved a CR (P = .11). Patients in remission received multiagent consolidation treatment, central nervous system prophylaxis, late intensification, and maintenance chemotherapy for a total of 24 months. After a median follow-up time of 43 months, the median survival for all 197 patients is 36 months; the median remission duration for the 167 CR patients is 29 months. Favorable pretreatment characteristics relative to remission duration or survival are younger age, the presence of a mediastinal mass or lymphadenopathy, a white blood cell count (WBC) less than 30,000/microL, L1 morphology, T or TMy immunophenotype, and the absence of the Ph chromosome. The estimates of the proportion surviving at 3 years are 69% for patients less than 30 years old, 39% for those 30 to 59 years old, 89% for those who had a mediastinal mass, 59% with WBC less than 30,000/microL, 63% with L1 morphology, 69% for T or TMy antigen expression, and 62% for those who lack the Ph chromosome. Fifteen patients (8%) had no unfavorable prognostic factors and have an estimated probability of survival at 5 years of 100% (95% confidence interval, 77% to 100%). This intensive chemotherapy regimen produces a high remission rate and a high proportion of durable remissions in adults with ALL.     

UREAPLASMAS UREALYTICUM AND HUMAN INFERTILITY: EFFECT ON SPERMATOZOA MORPHOLOGY

Seminal fluids of 197 males with complaints of involuntary infertility were examined for spermatozoal counts, morphological changes in the spermatozoa and cultured for ureaplasmas and mycoplasmas. In 12, no spermatozoa were present, 29 had a count of less than one million and 156 had more than one million spermatozoa per mL of the seminal fluid. Various morphological changes were detected in the spermatozoa in some cases. U urealyticum and M hominis were grown in 43.15% and 16.75% in comparison to control figures of 15.9% and 11.4% respectively. There was no correlation between growth of ureaplasmas and the spermatozoal count. Among the morphological changes, presence of coiled tails, presence of a fuzzy coat around the tail and microcolonies were highly specific for culture positivity (98.2, 98.2 and 97.35% respectively) but of low sensitivity (55.2%, 14.1% and 8.2% respectively).KEY WORDS: Mycoplasma, Spermatozoa, Ureaplasma     

OVARIAN HYPERSTIMULATION SYNDROME DURING INDUCTION OF OVULATION FOR INTRA UTERINE INSEMINATION

Ovarian Hyperstimulation Syndrome (OHSS) is a known iatrogenic complication of ovulation induction. Our experience of such complication while managing basic assisted conception cycles has been analysed in the present study. 12 such cases were identified in 976 cycles studied giving an overall incidence of 1.22%. All the cases were of mild to moderate variety and were managed conservatively. The duration of the complication ranged between 10 days to 6 weeks. Polycystic ovarian disease, LH: FSH ratio of more than 1, presence of four or more secondary follicles were found to be important predictive criteria. Identification of predictive factors of OHSS can be helpful in taking due care while using ovulation inducing drugs. Conception does worsen OHSS, but termination is usually not necessary.Key Words: OHSS, Ovulation Induction     

TO STUDY INCIDENCE OF CHLAMYDIAL GENITAL TRACT INFECTIONS USING ENZYME IMMUNO ASSAY-ANTIGEN DETECTION AND CELL CULTURE METHODS

Endocervical swabs from 315 patients were screened for chlamydial infection by using Enzyme Immuno Assay technique for antigen detection. Of these, 190 patients were of infertility and 125 patients were with history suggestive of pelvic inflammatory disease (PID). 100 age matched controls were also screened for the detection of chlamydial antigen by using EIA. The overall incidence of chlamydial infection in this study group was 15.2%. 21 (11.05%) of the infertility patients and 27 (21.6%) of the pelvic inflammatory disease cases were found to be positive for chlamydial antigen. The prevalence rate was found to be high in the age group of 31–40 years in both study groups i.e. infertility group (14.7%) and PID group (50%). All the ELISA positive cases (48) and randomly selected (10) age matched controls were screened by tissue culture using McCoy cell line. In the tissue culture, 44 of the 48 samples were found to be positive and none of the controls groups were found positive. 4 samples showed discordant results possibly due to the presence of non-viable organism or inhibitory material present at the sample site. The sensitivity and specificity of ELISA with respect to tissue culture are 100% and 71% respectively. The positive predictive value and the negative predictive value of the ELISA are 91.6% and 100% respectively. The efficiency of the test was found to be 93.1%.Key Words: Chlamydia trachomatis, Infertility, PID     

Expansion in vitro of retrovirally marked totipotent hematopoietic stem cells

A large number of biologic, technological, and clinical studies await the development of procedures that will allow totipotent hematopoietic stem cells to be expanded in vitro. Previous work has suggested that hematopoiesis can be reconstituted using transplants of cells from long- term marrow cultures. We have used retrovirus mediated gene transfer to demonstrate that marked totipotent hematopoietic stem cells are both maintained and can be amplified in such cultures, and then subsequently regenerate and sustain lympho-myeloid hematopoiesis in irradiated recipients. Marrow cells from 5-fluorouracil-treated male mice were infected with a recombinant virus carrying the neomycin resistence gene and seeded onto irradiated adherent layers of pre-established, long- term marrow cultures of female origin. At 4 weeks, cells from individual cultures were transplanted into single or multiple female recipients. Southern blot analysis of hematopoietic tissue 45 days posttransplantation showed retrovirally marked clones common to lymphoid and myeloid tissues in 14 of 23 mice examined. Strikingly, for 3 of 4 long-term cultures, multiple recipients of cells from a single flask showed marrow and thymus repopulation with the same unique retrovirally marked clone. These results establish the feasibility of retroviral-marking techniques to demonstrate the maintenance of totipotent lympho-myeloid stem cells for at least 4 weeks in the long- term marrow culture system and provide the first evidence of their proliferation in vitro. Therefore, such cultures may serve as a starting point for identifying factors that stimulate totipotent hematopoietic stem cell expansion.