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Background: Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for myelofibrosis. Driver mutations are the pathophysiological hallmark of the disease, but the role of mutation clearance after transplantation is unclear., Methods: We used highly sensitive polymerase-chain-reaction technology to analyze the dynamics of driver mutations in peripheral-blood samples from 324 patients with myelofibrosis (73% with JAK2 mutations, 23% with CALR mutations, and 4% with MPL mutations) who were undergoing transplantation after reduced-intensity conditioning. Mutations were detected before transplantation and at 30, 100, and 180 days after transplantation to measure clearance and its effect on relapse and cure. The two primary end points were relapse and disease-free survival., Results: At day 30 after transplantation, mutation clearance was found in 42% of the patients who had JAK2 mutations, 73% of those who had CALR mutations, and 54% of those who had MPL mutations; the corresponding percentages at day 100 were 63%, 82%, and 100%. The cumulative incidence of relapse at 1 year was 6% (95% confidence interval [CI], 2 to 10) among patients with mutation clearance at day 30 after transplantation and 21% (95% CI, 15 to 27) among those without mutation clearance at day 30. Disease-free and overall survival at 6 years were 61% and 74%, respectively, among patients with mutation clearance at day 30 after transplantation and 41% and 60%, respectively, among those without mutation clearance at day 30. Mutation clearance at day 30 appeared to outperform traditional donor chimerism as a measure of response; it was independently associated with a reduced risk of relapse or progression (hazard ratio, 0.36; 95% CI, 0.21 to 0.61) and appeared to overcome differences in prognosis based on the type of driver mutation ( JAK2 vs. MPL or CALR )., Conclusions: In patients with myelofibrosis, clearance of driver mutations at day 30 after transplantation appeared to influence relapse and survival, irrespective of the underlying driver mutation., (Copyright © 2025 Massachusetts Medical Society.)

We retrospectively analyzed high-risk ALL patients in CR1 receiving total body irradiation based conditioning regimen with ATLG (n = 74) or PTCy (n = 73) for GVHD prophylaxis. The 3-year OS and LFS were similar in both groups: 65 and 60% in the ATLG group and 64 and 67% in the PTCy group (p = 0.9 and 0.5, respectively). CIR and NRM rate at three years was 12 and 21% after PTCy and 19 and 20% after ATLG (p = 0.4 and p = 0.9, respectively). Acute GvHD grades II-IV and grades III/IV at 100 days was 46 and 19% after PTCy and 33 and 10% after ATLG (p = 0.08 and p = 0.9, respectively). Chronic GvHD of all grade at two years was higher after PTCy: 55% versus 26% (p < 0.001). Based on the propensity score matching (PSM) analysis, aGvHD grades II-IV was trending higher in the PTCy group compared to the ATLG group (p = 0.07). In contrast to the PSM analysis, on multivariate analysis the receipt of PTCy compared with ATLG was associated with a reduced CIR (p = 0.026). Our retrospective single-center analysis shows a lower incidence of acute and chronic GvHD while displaying similar LFS and OS after ATLG compared to PTCy in TBI based allogeneic stem cell transplantation for high-risk ALL., (© 2024. The Author(s).)

Acute kidney injury and chronic kidney disease is common in multiple myeloma. Fludarabine which is part of lymphodepletion before CAR-T cell therapy is renally eliminated and its use is not recommended for patients with severe renal impairment defined as a glomerular filtration rate below 30ml/min/1.73m 2 . We administered fludarabine to a 58-year-old female patient with myeloma-associated severe renal impairment as part of lymphodepletion before Idecabtagen vicleucel infusion. Fludarabine was administered in reduced dose (15mg/m 2 ) and cyclophosphamide with a dose of 300mg/m 2 followed by hemodialysis over six hours using a larger filter (FX-100). The therapy was well tolerated with excellent CAR-T cell expansion and complete remission which is ongoing now beyond 12 months., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marquard, Langebrake, Janson, Mahmud, Dadkhah, Kröger and Ayuk.)

Background: At increasing use of high-dose 5-fluorouracil-based chemotherapy for metastatic colorectal and gastric cancer complicated drug-induced colitis is observed more frequently. From May 1998 to November 2000 we observed 6 cases of 5-fluorouracil-induced colitis, in which we looked for involvement of small intestine. We report summing up on the 6 cases including both endoscopic and histological findings in both sites of the gut., Case Reports: In 2 men and 4 women (age 49-78 years) with advanced colon (n = 2), gastric (n = 3 ) and gallbladder (n = 1) cancer a palliative weekly high-dose infusional 5-fluorouracil (2,6 g/m(2)/24 h) and folinic acid (500 mg/m(2)/2 h) chemotherapy was performed. Few days after 1-5 chemotherapy courses the patients were admitted to our hospital with abdominal pain and partly severe watery diarrhea (up to 20 times evacuations/per day). The stool cultures were negative and there were no proof both of clostridium difficile and his toxin A and B. In 4 patients colonoscopy showed different grades of colitis up to diffuse erythema and microlesions, 2 patients had no visible lesions. In 4 patients endoscopy of the upper GI-tract showed a severe inflammation (n = 1) and a fibrinopurulent exsudate, severe edema and isolated ulcerations (n = 3) of jejunum after gastrectomy or duodenum with intact stomach. In the histological assessment different grades of 5-FU-induced colitis without (n = 2) or with (n = 4) involvement of the upper small intestine destruction of the superficial mucosa and crypts (epitheliumapoptosis) were found. 5 patients were treated by antibiotics (vancomycin n = 2, metronidazole n = 3), glucocorticoids (n = 5) and Saccaromyces cerevisiae (n = 3). After 8-10 days the patients were complete free of symptoms. One patient died due to the enterocolitis., Conclusions: The present cases demonstrate that high-dose 5-fluorouracil-based chemotherapy not only induces a colitis but also may involve the upper small intestine tract. Consequently, it represents an increasing and serious adverse event of high-dose chemotherapy. The etiology of the enterocolitis (drug- or bacterial-induced) needs further investigations in order to find a causal therapy and/or prophylaxis.

The aim of this study was to determine the incidence of complications of catheterization for total parenteral nutrition (TPN) in patients of the Parenteral Nutrition Unit of Groote Schuur Hospital. During the 2-year study period, 218 central venous catheters were inserted in 170 patients. The preferred technique of percutaneous infraclavicular subclavian venepuncture with subsequent subcutaneous tunnelling using a silicone elastomere catheter is described. The incidence of major complications of catheter insertion was 4,5% (pneumothorax 4, subclavian artery puncture 6). There was a 2,7% incidence of catheter malpositioning (requiring repositioning) at initial insertion. The mean duration of catheterization was 12,9 days. During this period there was a 6,9% incidence of mechanical complications (occluded lines 13, extravascular infusion 2). Catheter-related sepsis was suspected in 37 cases (16,9%) and all these catheters were removed, but in only 7 cases (3,2%) was the sepsis proved to be catheter-related. There was no correlation between the duration of catheterization and the development of catheter-related sepsis. Furthermore, there was no increase in the incidence of catheter sepsis in patients with sepsis before catheterization.

Total parenteral nutrition (TPN) carried out by the patient at home is a new concept in the treatment of intestinal failure. We describe a patient with Crohn's disease who has extensive involvement of the small intestine with resultant severe malabsorption, and who was therefore treated with 'home' TPN for 4 months. During this treatment there were no serious complications. The disabling symptoms present before hyperalimentation was commenced disappeared, and overall clinical improvement has been maintained for a further 6 months after TPN therapy. This case illustrates the feasibility of safe TPN at home in selected patients who have access to specialized hyperalimentation units.

Evidence is presented that monoclonal antibodies (mAb) against some human major histocompatibility complex (MHC) gene products and human sera containing HLA antibodies strongly inhibit immune phagocytosis of anti-D-sensitized red blood cells by human monocytes. w6.32HL, a mAb against a monomorphic class I antigen of high cell surface density, revealed the strongest inhibition among mAb reactive with MHC class I products. mAb with preferential reactivity for monomorphic and polymorphic DR and DQ epitopes (L203, L227, IIIE3, Tü22, Genox 3.53 and IV12) were noninhibitory. Definite inhibition was also apparent with a mAb against DRw52/MT2 (I-LR2) and with an antibody to class II antigens of high cell surface density (2MC3). Human sera containing HLA antibodies showed strong inhibition of immune phagocytosis up to a dilution of 1/1000. This inhibition could not be abrogated by platelet absorption. This indicates that human sera inhibiting immune phagocytosis may comprise at least two types of antibodies: cytotoxic HLA-specific antibodies which may or may not be inhibitory, and inhibitory antibodies against monocytic antigens not necessarily cytotoxic. These latter antibodies may recognize HLA DR or another as yet undefined gene product within, or closely associated to, the human MHC.

An interface for a high-performance liquid chromatographic system based on the Commodore 64 personal computer has been designed as an alternative to the expensive and somewhat inflexible solvent programmers and data acquisition systems offered by commercial manufacturers. The system consists of the Commodore 64 with a single disk drive and monitor, and an interface that directly controls the flow-rates of two Waters pumps for solvent delivery in either isocratic or gradient mode, as well as analog-to-digital conversion of chromatographic data and either graphic data output to a dot-matrix printer or digital-to-analog conversion for output to a chart recorder. The interface permits computer-controlled flow-rates of up to 10.0 ml/min, with an accuracy of 0.0047 ml/min at flow-rates of 4.1 ml/min and an accuracy of 0.03 ml/min at flow-rates of 10 ml/min. The software for data analysis permits tabulation of elution times and areas for the peaks in a chromatogram with an option for baseline correction. The data are stored on floppy disks together with information pertinent to the chromatogram (flow-rate, solvent composition, etc.).