Autologous Unpurged Bone Marrow Transplantation for Acute Non Lymphoblastic Leukemia in First Remission

Forty consecutive adult patients under the age of 50 with acute non-lymphoblastic leukemia (ANLL) in first complete remission, underwent autologous bone marrow transplantation (ABMT) between March 1984 and April 1990. The conditioning regimen employed included cyclophosphamide and total body irradiation, followed by the administration of unpurged ABMT. The median time from diagnosis to transplant was 7 months (3-15 months), and the median time from complete remission to ABMT was 4 months (range 3-9 months). Twenty-two (51%) patients remain in complete remission 6-81 months (median 24 months) after ABMT.

The causes of death were, recurrent leukemia (11 patients), parenchymal toxicities such as acute respiratory distress syndrome and veno-occlusive disease (3 patients), hemorrhage (2 patients) and infection (2 patients). Eleven patients relapsed after 3-12 months (median 5 months). This study has produced survival data comparable to those of other institutions employing TBI for either allo or autotransplants.     

Behavior of cryopreserved endothelial cells in different phases: Their application in the seeding of vascular prostheses

Various methods of cryopreservation of human endothelial cells (EC) were studied to determine their viability and behavior when seeded onto vascular prostheses made of polytetrafluoroethylene (PTFE). Three different protocols were used: (1) cyropreservation of whole umbilical vein, (2) cyropreservation of freshly extracted umbilical EC in suspension, and (3) cryopreservation of EC derived from a first subculture. Fresh EC and EC from a first subculture were used as controls. The viability and growth of these cells in culture media were studied, and basal prostacyclin levels were determined. The cells were assessed morphologically after they were seeded onto PTFE discs. Our results showed that the cryopreservation method that maintained the greatest viability was that in which previously cultured EC were used. Basal prostacyclin levels were significantly different following cyropreservation. However, when these cells were seeded onto PTFE discs their behavior was similar to that of fresh EC.We thank W. L. Gore & Associates for supplying the prostheses used in this study.Supported by a grant from the Comision Interministerial de Cieucia y Tecnologia SAF 92/0875.     

Subarachnoid lumbar drains: A case series of fractured catheters and a near miss

PURPOSE: Lumbar subarachnoid catheters for cerebrospinal fluid (CSF) drainage (lumbar drains) are indicated for several medical and surgical conditions. A number of complications can occur from the placement of this type of catheter, including catheter breakage from excessive traction or shearing over the Tuohy needle. CLINICAL FEATURES: Five cases of lumbar subarachnoid catheter breakage/shearing and catheter fragment retention, as well as one near miss, were identified over a one-year period at a single institution. All (n = 6) patients were undergoing neurosurgical procedures. Four patients required surgical retrieval of the catheter fragments. No patient experienced log-term neurological sequelae. DISCUSSION: From these experiences, the following risks factors for catheter rupture are identified: 1) intentional or accidental retraction of the catheter through the needle during placement; 2) faulty use of the guidewire; or 3) use of excessive force during removal of the catheter. Methods to prevent such complications are suggested, including minimal use, or complete avoidance of a guidewire.     

Feasibility of near real-time image-guided sinus surgery using intraoperative fluoroscopic computed axial tomography.

OBJECTIVE: One of the main limitations of image-guided surgery is that navigation relies on the use of a CT scan obtained before surgery and is unable to be updated during the procedure. A software addition has been developed to allow reconstruction of CT-like images from a series of fluoroscopic scans and integrate these into an image-guided system (GE Healthcare Surgical Navigation, Lawrence, MA). We report our initial experience with a series of patients undergoing intraoperative fluoroscopic navigation in sinus surgery. STUDY DESIGN AND SETTINGS: After institutional review board clearance, we prospectively studied 14 consecutive patients undergoing image-guided sinus surgery with the use of intraoperative fluoroscopy. RESULTS: All patients had preoperative and postoperative fluoroscopic images reconstructed into CT-like images. By the conclusion of the study, images were adequate in quality and accurate navigation was achieved. CONCLUSION: Real-time image-guided sinus surgery using fluoroscopy is feasible. Future studies will need to focus on defining the procedures that could benefit, such as tumor resection, to enhance patient safety during these operations.     

Autologous bone marrow transplantation as adjuvant treatment for high-risk Hodgkin's disease in first complete remission after MOPP/ABVD protocol.

Fifteen patients with very poor prognosis Hodgkin's disease in remission after MOPP/ABVD regimen, were treated with high-dose chemotherapy (HDC) and autologous marrow transplantation (ABMT) immediately after achieving complete remission (CR). Thirteen patients (86.6%) remain alive in unmaintained CR at a median time of 36 months (range 10-64 months) post-transplant. In the other two patients reasons for failure included relapse of Hodgkin's disease (one patient) and death due to interstitial pneumonitis secondary to carmustine therapy. These patients were compared with a historical control group consisting of 24 patients with the same poor prognostic factors, who achieved CR with MOPP/ABVD and did not receive other treatment. Eight out of 24 patients (33%) remain alive and well in unmaintained CR at a median time of 42 months (range 19-83 months). The administration of MOPP/ABVD combined with HDC and ABMT was not associated with an increased incidence of major toxicity. The results achieved support the early sequential treatment of a highly effective drug combination followed by HDC/ABMT that can substantially improve the likelihood of cure in these advanced stage very poor prognosis Hodgkin's disease patients.     

Characterization of circulating idiotypes containing immune complexes and their presence in the glomerular mesangium in patients with IgA nephropathy.

The possible pathogenic role for idiotype-anti-idiotype interactions in kidney diseases has recently been suggested. Since patients with IgA nephropathy often present antibodies against alimentary antigens, like bovine serum albumin (BSA), we isolated an idiotypic antibody with BSA specificity from one of these patients. By means of a specific anti-idiotypic antibody raised in rabbits, we have studied the participation of these idiotypes in circulating and renal deposited immune complexes (IC) in patients with IgA nephropathy. On indirect immunofluorescence, the presence of cross-reactive idiotypes was detected in the glomeruli of 12 out of 42 (28%) patients with IgA nephropathy, but in none of 15 membranous or mesangiocapillary nephritis examined. The staining was located within mesangial and paramesangial areas, with a similar, but less intensive, pattern distribution than IgA. Previous adsorption of rabbit anti-idiotype antibodies on an idiotype-Sepharose column completely abolished that staining. A close relationship was found between the presence of cross-reactive idiotypes on mesangial immunoglobulins and the existence of increased levels of serum idiotypes and idiotype-containing IC. Serum analytical ultracentrifugation showed that circulating IC containing idiotypes have chiefly a large (greater than 19 S) and intermediate (13 S-19 S) size, while those containing anti-BSA antibodies were only between 7 S-13 S fractions, or absent. Our results suggest that in patients with IgA nephropathy, shared idiotypes participate in the formation of circulating and renal deposited IC. It is possible that the apposition of free anti-idiotype to idiotype already bound to glomeruli, and vice versa, could contribute to increasing the amount and size of mesangial immune deposits, and, therefore, facilitate or perpetuate tissue injury.     

Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: long-term results by the NHLCSG.

BACKGROUND: There is not univocal concordance for using high-dose sequential therapy (HDS) as first-line treatment for aggressive non-Hodgkin's lymphoma (NHL). We designed this study to evaluate the usefulness of HDS followed by high-dose therapy (HDT) with autologous stem cell transplantation as front-line treatment in different subsets of aggressive NHL. PATIENTS AND METHODS: Among 223 patients aged 15-60 years with aggressive, advanced stage NHL, 106 patients were randomized to VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) for 12 weeks (plus HDS/HDT in case of persistent disease) (arm A), and 117 patients to VACOP-B for 8 weeks plus upfront HDS/HDT (arm B). RESULTS: According to the intention-to-treat analysis, the complete response rate was 75% for arm A and 72.6% for arm B. With a median follow-up of 62 months there was no difference in 7-year probability of survival (60% and 57.8%; P = 0.5), disease-free survival (DFS) (62% and 71%; P = 0.2) and progression-free survival (PFS) (44.9% and 40.9%; P = 0.7) between the two arms. Subgroup analyses confirmed that the best results in terms of survival, DFS and PFS were achieved by patients with large B-cell NHL without bone marrow (BM) involvement, independently of the treatment arm. Results were poorer in other categories of patients and poorest in patients with BM involvement. CONCLUSIONS: Aggressive NHL patients do not benefit from upfront HDS/HDT.     

Differences in the causes of death of HIV-positive patients in a cohort study by data sources and coding algorithms

OBJECTIVES:: To compare causes of death (CoDs) from two independent sources: National Basic Death File (NBDF) and deaths reported to the Spanish HIV Research cohort [Cohort de adultos con infección por VIH de la Red de Investigación en SIDA CoRIS)] and compare the two coding algorithms: International Classification of Diseases, 10th revision (ICD-10) and revised version of Coding Causes of Death in HIV (revised CoDe). METHODS:: Between 2004 and 2008, CoDs were obtained from the cohort records (free text, multiple causes) and also from NBDF (ICD-10). CoDs from CoRIS were coded according to ICD-10 and revised CoDe by a panel. Deaths were compared by 13 disease groups: HIV/AIDS, liver diseases, malignancies, infections, cardiovascular, blood disorders, pulmonary, central nervous system, drug use, external, suicide, other causes and ill defined. RESULTS:: There were 160 deaths. Concordance for the 13 groups was observed in 111 (69%) cases for the two sources and in 115 (72%) cases for the two coding algorithms. According to revised CoDe, the commonest CoDs were HIV/AIDS (53%), non-AIDS malignancies (11%) and liver related (9%), these percentages were similar, 57, 10 and 8%, respectively, for NBDF (coded as ICD-10). When using ICD-10 to code deaths in CoRIS, wherein HIV infection was known in everyone, the proportion of non-AIDS malignancies was 13%, liver-related accounted for 3%, while HIV/AIDS reached 70% due to liver-related, infections and ill-defined causes being coded as HIV/AIDS. CONCLUSION:: There is substantial variation in CoDs in HIV-infected persons according to sources and algorithms. ICD-10 in patients known to be HIV-positive overestimates HIV/AIDS-related deaths at the expense of underestimating liver-related diseases, infections and ill defined causes. CoDe seems as the best option for cohort studies.