Management of superficial upper tract transiotional cell carcinoma using holmium:YAG laser and endoscopic surveillance

In der vorliegenden retrospektiven Studie wurde die Effektivität der ureteroskopischen Therapie des Urothelkarzinoms des oberen Harntraktes in Kombination mit endoskopischer Nachsorge in regelmäßigen Abständen untersucht. Das vorgestellte Vorgehen entspricht dem der stadiengerechten Therapie der oberflächlichen Harnblasenkarzinome durch die TUR-B. Von Mai 1995 bis Juli 2001 wurden 22 Patienten mit 24 erkrankten oberen Harntrakten (20 pTa und 2 pT1Karzinome) endoskopisch mit Tumorvaporisation durch Holmiumlaser therapiert und endoskopisch nachverfolgt. Zwei Patienten waren einnierig bzw. funktionell einnierig, sieben Patienten hatten eine Restniere bei Urothelkarzinom des kontralateralen oberen Harntraktes und zwei Patienten ein bilaterales Urothelkarzinom. Die Evaluation und Therapie umfasste eine retrograde röntgenologische Darstellung des betroffenen oberen Harntraktes, die Ureterorenoskopie mit 7,5F und 8,5F flexiblen und semirigiden Ureterorenoskopen mit Entnahme einer Spülzytologie und Biopsie repräsentativen Tumorgewebes sowie die Laservaporisation der Tumore. Die Nachsorge erfolgte ureterorenoskopisch, die Intervalle (3 oder 6 Monate) waren abhängig von der Dauer der Rezidivfreiheit. Bei 107 der 186 Ureterorenoskopien erfolgte die Abtragung eines oder mehrerer Tumoren, wovon bei 80 Ureterorenoskopien Rezidive bzw. persistierende Urothelkarzinome behandelt wurden. In nur knapp 3% (3 von 107 Operationen) traten operationsbedingte schwere Komplikationen auf. Das mediane Follow-up aller Patienten betrug 44 Monate (3-116 Monate). 45,5% der Patienten (10 obere Harntrakte) blieben in der weiteren Nachbeobachtung tumorfrei. In zwei Harntrakten entwickelten sich nach 18 bzw. 22 Monaten Rezidivtumoren. In zwölf oberen Harntrakten (50%) konnte keine längerfristige Tumorfreiheit erzielt werden. Bei insgesamt acht harnableitenden Systemen (33,3%) konnte durch eine wiederholte ureterorenoskopische Therapie die Notwendigkeit zur Hämodialyse im Mittel um fast fünf Jahre aufgeschoben werden. Insgesamt erfolgten sieben Nephrektomien. Im Laufe des Follow-up verstarben tumorassoziiert drei Patienten bei gleichzeitig vorliegenden Harnblasenkarzinomen. Eine organerhaltende ureterorenoskopische Therapie oberflächlicher Urothelkarzinome des oberen Harntraktes mit standardisierter postoperativer endoskopischer Nachsorge ist im klinischen Alltag durchführbar. Voraussetzung ist eine ausreichende Compliance der Patienten. Unverzichtbar in der Nachsorge ist die Ureterorenoskopie. Aufgrund des hohen Rezidivpotentials kann nur ein Teil der Patienten kurativ behandelt werden. Bei sorgfältig selektionierten Patienten bietet die endoskopische Therapie mit dem Holmiumlaser aufgrund der Eignung zur wiederholten Behandlung die Möglichkeit, die Dialyse über Jahre hinweg zu vermeiden. Eine Verschlechterung der Prognose quoad vitam durch eine solche palliative Therapie ließ sich in unserem Krankengut nicht nachweisen.In the retrospective study we investigated the long-term outcome of patients who underwent endoscopic surgery of non superficial upper tract transitional cell carcinoma (UTTCC) and endoscopic surveillance. This management corresponds to the current standard treatment of non invasive bladder cancer. The standard operative procedure for UTTCC is the nephroureterectomy with partial cystectomy at the affected ureteral orifice. From May 1995 to July 2001 22 patients (20 pTa and 2 pT1) with 24 renal units (RU) were treated by ureteroscopic holmium YAG:laser vaporisation of superficial UTTCC and underwent endoscopic surveillance. 2 patients had solitary kidneys or functionally solitary kidneys. 7 patients had solitary kidneys with a history of nephroureterectomy for UTTCC. 2 patients suffered from bilateral disease. Evaluation and therapy included retrograde ureteropyelography, semirigid and flexible ureteropyeloscopy, cytology of upper tract washings, ureterorenoscopic inspection and biopsy as well as ablation of tumours by holmium laser. The surveillance was performed ureteroscopically (4 to 6 weeks, if the primary tumour resection was not complete, every 3 months or every 6 months, if there was no recurrence in two consecutive follow-ups). A total of 186 ureteroscopys were performed, 107 of these requiring laser ablations of one or multiple tumours. 80 laser treatments had to be done because of recurrent or persistent UTTCC. Therapy related major complications were rare (3 of 107). Median follow up was 44 months (range 3-116). 10 RU (45.5%) remained tumor free. Recurrent tumors developed in two RU after a follow-up of 18 and 22 months. There were recurrent or persistent tumours in the most ureteroscopic follow-ups in 12 upper urinary tracts (50%). Endoscopic surveillance and therapy of recurrences allowed for avoidance of haemodialysis in 6 and delay thereof in 2 patients. The mean duration of kidney preservation was five years. A total of 7 patients underwent nephroureterectomy during the follow up. 3 Patients suffering from concurrent bladder cancer died from transitional cell carcinoma. Kidney preservation by ureteroscopic therapy of UTTCC with closed follow up is possible in clinical routine provided the patient is compliant as ureterorenoscopy in regular intervals is essential in surveillance. Most of the patients had an upper tract recurrence. Thus only a fraction of the patients can be treated curatively. In carefully selected patients the laser ablation of UTTCC offers avoiding renal replacement therapy because of its potential of recurrence treatment. No worsening of prognosis was seen in those patients

Prognosis of patients with primary central nervous system lymphoma after high-dose chemotherapy followed by autologous stem cell transplantation

High-dose chemotherapy followed by autologous stem cell transplantation has been shown to be feasible and highly effective in newly diagnosed primary central nervous system lymphoma. In this retrospective multicenter study, we investigated prognosis and baseline risk factors in patients with primary central nervous system lymphoma who underwent this treatment approach. We retrospectively analyzed 105 immunocompetent patients with primary central nervous system lymphoma who underwent high-dose chemotherapy followed by autologous stem cell transplantation with or without whole brain radiotherapy as first-line consolidation treated at 12 German centers between 1997 and 2011. We estimated survival rates and investigated the impact of age, performance status, serum lactate dehydrogenase level, and deep brain involvement on overall and progression-free survival. Patients were additionally categorized into three prognostic groups according to the Memorial Sloan Kettering Cancer Center prognostic model. After a median follow up of 47 months, median progression-free survival and overall survival was reached after 85 and 121 months; 2- and 5-year survival rates were 82% and 79%, respectively. The Memorial Sloan Kettering Cancer Center prognostic model did not predict survival. Only age revealed some evidence of prognostic relevance. Overall response rate was 95%; of those patients with progressive disease before high-dose chemotherapy, 7 of 20 achieved ongoing complete remission after therapy without whole brain radiation therapy. Transplantation-associated mortality was 2.8%. High-dose chemotherapy followed by autologous stem cell transplantation is a highly effective and safe treatment modality for selected primary central nervous system lymphoma patients. Superiority compared to standard chemotherapy still warrants further investigation

ADAMTS13 and VWF activities guide individualized caplacizumab treatment in patients with aTTP

Introduction of the nanobody caplacizumab was shown to be effective in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP) in the acute setting. The official recommendations include plasma exchange (PEX), immunosuppression, and the use of caplacizumab for a minimum of 30 days after stopping daily PEX. This study was a retrospective, observational analysis of the use of caplacizumab in 60 patients from 29 medical centers in Germany. Immunosuppressive treatment led to a rapid normalization of ADAMTS13 activities (calculated median, 21 days). In 35 of 60 patients, ADAMTS13 activities started to normalize before day 30 after PEX; in 11 of 60 patients, the treatment was extended beyond day 30; and in 5 patients, it was extended even beyond day 58 due to persistent autoimmune activity. In 34 of 60 instances, caplacizumab was stopped before day 30 with a favorable outcome whenever ADAMTS13 activities were >10%. In contrast, 11 of 34 patients with ADAMTS13 activities <10% at the time of stopping caplacizumab treatment developed a nonfavorable outcome (disease exacerbation or relapse). In some cases, prolongation of the treatment interval to every other day was feasible and resulted in a sustained reduction of von Willebrand factor activity. ADAMTS13 activity measurements are central for a rapid diagnosis in the acute setting but also to tailor disease management. An ADAMTS13 activity-guided approach seems safe for identifying the individual time point when to stop caplacizumab to prevent overtreatment and undertreatment; this approach will result in significant cost savings without jeopardizing the well-being of patients. In addition, von Willebrand factor activity may serve as a biomarker for drug monitoring

Real-world data confirm the effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura

Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare but life-threatening condition. In 2018, the nanobody caplacizumab was approved for the treatment of adults experiencing an acute episode of aTTP, in conjunction with plasma exchange (PEX) and immunosuppression for a minimum of 30 days after stopping daily PEX. We performed a retrospective, observational analysis on the use of caplacizumab in 60 patients from 29 medical centers in Germany during acute disease management. Caplacizumab led to a rapid normalization of the platelet count (median, 3 days; mean 3.78 days). One patient died after late treatment initiation due to aTTP-associated complications. In 2 patients with initial disease presentation and in 4 additional patients with laboratory signs of an exacerbation or relapse after the initial therapy, PEX-free treatment regimens could be established with overall favorable outcome. Caplacizumab is efficacious in the treatment of aTTP independent of timing and ancillary treatment modalities. Based on this real-world experience and published literature, we propose to administer caplacizumab immediately to all patients with an acute episode of aTTP. Treatment decisions regarding the use of PEX should be based on the severity of the clinical presentation and known risk factors. PEX might be dispensable in some patients

Real-world experience of CPX-351 as first-line treatment for patients with acute myeloid leukemia

To investigate the efficacy and toxicities of CPX-351 outside a clinical trial, we analyzed 188 patients (median age 65 years, range 26-80) treated for therapy-related acute myeloid leukemia (t-AML, 29%) or AML with myelodysplasia-related changes (AML-MRC, 70%). Eighty-six percent received one, 14% two induction cycles, and 10% received consolidation (representing 22% of patients with CR/CRi) with CPX-351. Following induction, CR/CRi rate was 47% including 64% of patients with available information achieving measurable residual disease (MRD) negativity (<10(-3)) as measured by flow cytometry. After a median follow-up of 9.3 months, median overall survival (OS) was 21 months and 1-year OS rate 64%. In multivariate analysis, complex karyotype predicted lower response (p = 0.0001), while pretreatment with hypomethylating agents (p = 0.02) and adverse European LeukemiaNet 2017 genetic risk (p < 0.0001) were associated with lower OS. Allogeneic hematopoietic cell transplantation (allo-HCT) was performed in 116 patients (62%) resulting in promising outcome (median survival not reached, 1-year OS 73%), especially in MRD-negative patients (p = 0.048). With 69% of patients developing grade III/IV non-hematologic toxicity following induction and a day 30-mortality of 8% the safety profile was consistent with previous findings. These real-world data confirm CPX-351 as efficient treatment for these high-risk AML patients facilitating allo-HCT in many patients with promising outcome after transplantation