Rearrangement of the MLL gene confers a poor prognosis in childhood acute lymphoblastic leukemia, regardless of presenting age

MLL gene rearrangements are associated with an extremely poor prognosis in infants with acute lymphoblastic leukemia (ALL), but little is known about their clinical significance in older children. Therefore, we studied 45 cases of childhood ALL with abnormalities of chromosome 11q23 for rearrangement of the MLL gene to determine if this feature confers a uniformly poor prognosis. MLL gene rearrangements were detected in all 18 cases with the common t(4;11), t(9;11) or t(11;19) translocations, whereas only 5 of 12 patients with either unbalanced or uncommon balanced translocations demonstrated a rearrangement. Abnormalities of the MLL gene were not detected in any of the 15 cases with a deletion or inversion of the chromosomes 11q23 region. The presence of an MLL rearrangement was significantly associated with age less than 1 year (P < .001), leukocyte count >50 x 10(9)/L (P = .003), and the absence of leukemic cell CD10 expression (P < .001). In a stratified statistical analysis adjusted for age and treatment protocol, MLL gene rearrangement was correlated with an inferior treatment outcome (P = .028). The 4-year event-free survival estimate (+/- SE) was 10% +/- 6.5% for cases with a rearranged MLL gene and 64% +/- 19.2% for other cases. When infants were excluded from the analysis, MLL rearrangement was still significantly associated with a poor outcome (P = .02), and remained so with the exclusion of t(4;11)- positive cases (P = .05). Thus, regardless of presenting age, MLL gene rearrangement identifies a high-risk subgroup of patients who are not likely to be cured with conventional treatment.     

Clinical significance of CD34 expression in childhood acute lymphoblastic leukemia

The CD34 antigen was detected on > or = 10% of the blast cells in 235 (70%) of 335 cases of newly diagnosed childhood acute lymphoblastic leukemia (ALL) treated in two consecutive chemotherapy trials. By immunophenotype, the distribution of positive cases favored early pre-B ALL (83%; n = 180) followed by pre-B ALL (61%; n = 89) and then T-cell ALL (46%; n = 61) (P < .001). Among the B-lineage cases, CD34 expression was significantly associated with favorable presenting features: age 1 to 10 years, white race, absence of central nervous system (CNS) leukemia, low serum lactate dehydrogenase level, CD10 expression, and leukemic cell hyperdiploidy (> 50 chromosomes or DNA index > or = 1.16). Event-free survival was clearly superior for patients with CD34+ leukemia (P = .01), with an estimated 83% +/- 6% (SE) of the cohort remaining free of adverse events at 5 years post diagnosis, as compared to 63% +/- 10% of the group without this feature. Multivariate analysis showed that the prognostic influence of the antigen was independent of age, leukocyte count, and other well- recognized factors, suggesting that it would add discriminatory power to current systems of risk assignment. Findings in T-cell ALL were the reverse: CD34 expression showed positive correlations with initial CNS leukemia and CD10 negativity but not with any good-risk presenting characteristics. Log-rank analysis indicated no adverse effect on treatment outcome by CD34 antigen expression, although additional patients with need to be studied to obtain a definitive answer. The opposed clinical associations of CD34 expression in B- and T-lineage ALL may reflect fundamental biologic differences between these leukemia species.     

Hypodiploidy is associated with a poor prognosis in childhood acute lymphoblastic leukemia

Leukemic cells from 31 (7.6%) of 409 children with newly diagnosed acute lymphoblastic leukemia (ALL) had a hypodiploid karyotype. The patients' ages ranged from 0.8 to 17 years (median, 5 years) and their initial leukocyte counts from 1.0 to 132 X 10(9)/L (median, 12.7 X 10(9)/L). Modal chromosome numbers for the leukemic stem lines were 45 in 26 cases, 28 in two cases, and 26, 36 and 43 in one case each. Seven cases had one to three additional abnormal lines due to clonal evolution. Chromosome 20 was lost most frequently (nine cases). Structural abnormalities--including chromosomal translocations (21 cases), deletions (ten cases), duplications (two cases), or inversions (one case)--were common findings; the nonrandom translocations consisted of the t(1;19)(q23;p13.3) in two pre-B cases and tdic(9;12)(p1?1;p1?2) in three cases of common ALL. When compared with hyperdiploid cases (greater than 50 chromosomes), ALL with hypodiploidy was found to have a poorer outcome and was more likely to be associated with chromosomal translocations, higher serum lactic dehydrogenase levels, and age less than 2 or greater than or equal to 10 years. Moreover, patients with hypodiploid ALL fared as poorly as those with pseudodiploid karyotypes, even though their leukocyte counts and serum lactic dehydrogenase levels were lower and they had a comparable frequency of leukemic cell translocations. Hypodiploidy is therefore an unfavorable karyotypic feature in childhood ALL.     

POSTOPERATIVE ANALGESIA: A LOCAL SOLUTION

A simple, safe, and effective technique of postop analgesia using wound perfusion with bupivacaine 0.25% via an indwelling intracatheter inserted in the depth of the wound was carried out on 25 ASA grade I/II patients of varying age groups reporting for a variety of surgical procedures. The first dose was given prior to shifting the patient from the OT. Subsequent doses were administered on patient demand basis. The intracatheter was kept in position for 48–72 hours postop. An analysis was made on the patients'' pain relief using a visual analogue scale, dose/frequency of bupivacaine required, dose/type of supplemental analgesia needed, haemodynamic changes during infiltration, wound healing, and patient satisfaction. In this study only 12% of patients required opioids on Day One postoperatively. There were no adverse effects of infiltration either systemically or on wound healing, and all the patients had excellent postop analgesia.KEY WORDS: Analgesia, Bupivacaine, Postoperative, VAS     

Postoperative spasm of mammary-coronary grafts and possibilities of its correction by dihydropyridine calcium antagonists nifedipine and amlodipine

AIM: To assess efficacy of dihydropyridine calcium antagonists nifedipine and amlodipine for prevention of spasm of internal mammary artery after mammary-coronary bypass grafting. MATERIAL AND METHODS: Eighty eight men (age 56,5-/+7.2 years) subjected to mammary-coronary grafting were randomized to 3 groups. Patients of group 1 (n=35) received nifedipine (10 mg t.i.d.), patients of group 2 (n=30) received amlodipine (5 mg o.d.) and patients of group 3 (n=23) did not receive calcium antagonists. The following parameters were studied: mean linear and volume velocity of blood flow, graft lumen diameter, systolic-diastolic index. Dynamics of flow was assessed during 2 weeks after surgery. RESULTS: In nifedipine treated patients blood flow through grafts to posterior interventricular, anterior interventricular, anterior interventricular and diagonal branches rose by 61.2, 37.4, and 102.9%, respectively. In amlodipine treated patients these figures were 103.4, 113.1 and 147.1%, respectively. Treatment with nifedipine was associated with decrease of graft systolic-diastolic index by 20.2, 20.7, 19.9%, respectively, treatment with amlodipine--by 27.3, 20.6, 32.9%, respectively. Lumen diameter of grafts to posterior interventricular, anterior interventricular, anterior interventricular and diagonal branches in nifedipine treated patients increased by 9.5, 17.6, and 7.7%, respectively, in amlodipine treated patients--by 20, 22.7, and 25.9%, respectively. Moreover amlodipine was better tolerated. CONCLUSION: The first dose of nifedipine and amlodipine increased diameter of mammary-coronary grafts and blood flow through them. Augmentation of these effects which occurred during further use of nifedipine and amlodipine for 2 weeks was milder and more gradual in amlodipine treated patients.     

Gated MR imaging of the heart: intracardiac signals in patients and healthy subjects

The appearance of intraluminal signal in the cardiac chambers, the descending aorta, and blood vessels was studied in healthy subjects and patients with myocardial disease on first and second spin-echo gated magnetic resonance images. Signal was present in the cardiac chambers and the aorta at various phases of the cardiac cycle when physiological or pathological slow flow conditions are expected in healthy subjects and in patients. Healthy individuals tended to show signal in the ventricles and aorta during end-diastole, and signal was less likely to be present at higher heart rates and in systolic images. In patients with regional or global left ventricular dysfunction, intraventricular signal tended to persist into systole. Surprisingly, intraventricular signal was not present with increased frequency adjacent to infarcted regions of the myocardial wall. Thus, the mere presence of intracavitary signal cannot be used as an indicator of either regional or global cardiac contraction abnormalities. In the left atrium, signal was often present during systole. Physical factors determining the appearance of signal of flowing blood are discussed in an Appendix.