The identification of recurring chromosomal translocations has provided clues to the gene regions important in lymphoma development. Among 157 patients with non-Hodgkin lymphoma studied by cytogenetic analysis, four new recurring translocations have been identified--t(8;9) (q24;p13), t(11;18)(q21;q21), t(14,15)(q32;q15), and an unbalanced translocation giving rise to der(22)t(17;22) (q11;p11). Each translocation appeared twice. The t(11;18) was the only karyotypic abnormality in the two patients with it, and the t(14;15) was the sole karyotypic abnormality in one patient. All translocations were found in B-cell malignancies and were associated with both nodal and extranodal disease. Among the regions affected, only the immunoglobulin heavy- chain gene MYC, and BCL2, have thus far been associated with lymphoma. The breakpoint sites identified by these translocations warrant further investigation at the molecular level.

The fracture behavior of the silicon/Pyrex glass anodic bond was investigated using the methods of linear elastic bimaterial fracture mechanics. Due to the high bond strength, interfacial cracks were invariably observed to kink away from the interface into the more compliant glass under approximately mode I remote tensile loading. Kink angles measured by profilometry increased from 14 to 28°as bonding temperature increased from 300 to 450 °C. A regime of stable cracking accompanied penetration of cracks into the glass, with maximum load and corresponding fracture toughness measurement occurring at a location significantly removed from the interface. Approximately mode I, near-interface, plane-strain fracture toughness values (KIC) measured by rising load testing of chevron-notched and straight-thru-cracked compact-tension specimens increased from 0.63 to 0.68 MPa-m1/2 and 0.66 to 0.75 MPa-m1/2, respectively, as bonding temperature increased from 300 to 450 °C. In addition, XPS measurements revealed a sodium depletion zone of decreasing size and depletion magnitude with increasing bonding temperature over the same range. The near-interface region of the glass also experiences compressive residual stresses which decrease linearly with distance from the interface according to linear elastic computations. These stresses increase in magnitude with increasing bonding temperature due to enhanced differential thermal contraction upon cooling to room temperature. It is proposed that the trends in toughness and in kink angle with bonding temperature can be at least partially accounted for by variation of crack-tip shielding with compressive residual stress magnitude, the effects of interfacial. crack-tip shear stresses induced by the thermal mismatch, and by an increase in Young's modulus of the near-interface glass accompanying sodium depletion.

This paper presents the development of a higher-order direct boundary integral-displacement discontinuity method for crack propagation in layered elastic materials. The method is based on the dual boundary integral equations of linear elasticity which are solved by means of a quadratic boundary element formulation. The analytical solution for a point force within a bonded half-plane region is used to derive the kernel functions of the boundary integral equations. Square-root displacement-discontinuity elements are used to model the crack tips, and stress intensity factors may be computed using the numerically predicted values of the displacement discontinuity components at the midpoints of these crack-tip elements. An algorithm based on the maximum tensile-stress criterion is then developed and incorporated into the boundary element model to predict the paths of cracks propagating in layered elastic materials.In the experimental part of this study, crack profiles for straight-through-cracked, compact-tension specimens of the anodically bonded silicon/Pyrex glass system are measured by profilometry. The plane strain prediction of the crack-propagation path is compared with the experimentally measured crack profiles. Consistent with the prediction, the interfacial crack is observed to kink away from the strong, anodicaUy-bonded interface and propagate into the more compliant glass layer. The predicted initial kink angle of 26 ° agrees very well with the average measured value of 280 . The measured path of the crack is also in very good agreement with the predicted path over about the first 120 microns of crack growth with increasing deviation observed beyond that.

Although many recurring chromosome abnormalities have been found in malignant lymphoma (ML) in recent years, their relationship to histology remains largely undefined. We have correlated, in the same tumor mass, chromosome findings with histology, defined by the International Working Formulation for Clinical Usage, in 120 patients. We find differences among histologies in the frequency of normal metaphases and the modal number of the predominant abnormal clone. In addition, most histologies have been significantly (P less than .01) associated with specific chromosome abnormalities. In particular, ML, follicular, predominantly small cleaved cell was associated with t(14;18)(q32;q21); ML, follicular, mixed small cleaved cell and large cell with t(14;18)(q32;q21) and trisomy 8; ML, follicular, predominantly large cell with trisomy 7 and breaks in 17q21-q25; ML, diffuse, mixed small cell and large cell with breaks in 11p; ML, diffuse, large cell with trisomy 21 and breaks in 2q and 9q; ML, large cell, immunoblastic with breaks at 6q21; and ML, small noncleaved cell with t(8;14)(q24;q32). Only the associations with t(14;18) and t(8;14) have been previously reported. The associated chromosome abnormality usually occurred in 30% to 70% of a given histology, raising the possibility that cytogenetics may add important prognostic information in lymphoma as it does in the acute leukemias.

Summary:We report a patient with pre-existing end-stage renal disease (ESRD) who underwent successful matched related donor allogeneic bone marrow transplantation for AML in second complete remission (CR2) using conditioning with high-dose cyclophosphamide (CY, 60 mg/kg/day ؋ 2) and TBI (165 cGy twice daily ؋ 4 days). The timing of hemodialysis after high-dose CY was extrapolated from available data on the pharmacokinetics of high-dose CY and hemodialysis clearance of conventional dose CY and its metabolites. Pharmacokinetic analyses indicated that the elimination of highdose CY and its alkylating metabolites is impaired in ESRD but is cleared with hemodialysis. The patient's early post-transplant course was uncomplicated, and WBC and platelet engraftment occurred by day ؉22. Bone marrow examination on day ؉25 showed trilineage engraftment with no AML; cytogenetics showed 100% donor karyotype. The patient remains in remission with 100% donor karyotype at 3 years post transplant. Clinical results indicate that the administration of high-dose CY is feasible with hemodialysis support for patients with ESRD. Keywords: allogeneic BMT; renal disease; cyclophosphamide; AML; pharmacokinetics; hemodialysis High-dose chemotherapy with BMT is considered to be contraindicated in patients with severe renal dysfunction since it is often assumed that the pharmacokinetics and/or pharmacodynamics of high-dose chemotherapy are significantly altered. High-dose cyclophosphamide (CY) is a common component of preparative regimens. The effect of renal dysfunction on the pharmacokinetics of high-dose CY is not known although pharmacokinetic models suggest that Correspondence: Dr JJ Perry, Section of Hematology/Oncology, Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA 27157 Received 9 July 1998; accepted 12 November 1998 clearance of two important CY metabolites, 4-OH CY and aldophosphamide, may be reduced if severe renal impairment is present.1 The pharmacokinetics of conventionaldose CY and its alkylating metabolites are altered in patients with renal insufficiency.2,3 However, the toxicity profile has not been reported to be different from patients with normal renal function 4 leading some authors to suggest that conventional doses of CY do not require modification in patients with renal dysfunction. 5 In this report, we describe the clinical BMT course of a patient with endstage renal disease (ESRD) (on chronic hemodialysis) and AML in CR2 who received high-dose CY. The pharmacokinetics of high-dose CY and CY-alkylating metabolites are also presented. Case reportA 42-year-old male was diagnosed with AML (subtype FAB-M2) in January 1994. He achieved CR after treatment with daunorubicin 45 mg/m 2 i.v. × 3 days and cytarabine 100 mg/m 2 /day by continuous i.v. infusion (CIVI) ϫ 7 days. He was given four courses of post-remission therapy using daunorubicin 45 mg/m 2 i.v. ϫ 2 days and cytarabine 100 mg/m 2 /day CIVI ϫ 5 days, completed in July 1994. ...