PURPOSE: The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990.MATERIALS AND METHODS: Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,542 patients with complete information on potentially relevant variables. The results were validated in an independent data set.RESULTS: Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided ( https://www.eortc.org/IGCCCG-Update ).CONCLUSION: The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.

Background: Castleman disease (CD) encompasses a spectrum of rare disorders with characteristic histopathological features. Unicentric CD (UCD) is a benign, local hyperplasia of lymphoid tissue that is usually curable. Multicentric CD (MCD) manifests as a potentially life-threatening systemic disease with complex symptomatology which is mostly due to an overproduction of interleukin-6 (IL-6) or dysregulation of IL-6-related signaling pathways. From a therapeutic perspective, it is important to distinguish idiopathic MCD (iMCD) from those cases that are associated with the human herpesvirus-8 (HHV-8 + MCD). Summary: During recent years, it has become increasingly clear that even HHV-8-negative MCD is not a homogeneous entity and that there are clinically distinct variants. International consensus guidelines for diagnosis and treatment have been developed for iMCD and UCD. Key Messages: We herein summarize recent advances in diagnosis, treatment, and novel insights into the pathogenesis of this disease.

Lung cancer is the leading cause of cancer death in HIV-infected persons. Overall, the prognosis is poor, with long-term survival reported only for patients with limited stage disease [1]. Checkpoint inhibitors have significantly improved outcomes in patients with metastatic non-small-cell lung cancer (NSCLC). However, there is only very limited data on their use in HIV-related NSCLC [2].

Hemophagocytic lymphohistiocytosis (HLH) is a rare but often fatal hyperinflammatory syndrome caused by an inborn or acquired error of immunity. In adults, the underlying immunodeficiency generally arises alongside severe infections, malignancies, autoimmune diseases, and immunosuppressive treatment. To analyze risk factors and outcome in adults, we conducted a multicenter retrospective study. A total of 62 adult (age ≥18 years) patients met at least one of the following inclusion criteria: (1) ≥5 of 8 HLH-2004 criteria, (2) HScore ≥ 200 plus 4 HLH-2004 criteria, or (3) mutation compatible with an HLH diagnosis. Most patients (65%) were male, and the median age at diagnosis was 53.5 years (range, 19-81 years). All patients were assigned to 4 etiologic subgroups based on their most likely HLH trigger. The survival probability of the 4 etiologic subgroups differed significantly (P = .004, log-rank test), with patients with an underlying malignancy having the worst clinical outcome (1-year survival probability of 21%). The parameters older age, malignant trigger, elevated serum levels of aspartate transferase, creatinine, international normalized ratio, lactate dehydrogenase, sCD25, and a low albumin level and platelet count at treatment initiation were significantly (P < .1) associated with worse overall survival in the univariate Cox regression model. In multivariate analysis, sCD25 remained the only significant prognostic factor (P = .005). Our results suggest that sCD25 could be a useful marker for the prognosis of patients with HLH that might help to stratify therapeutic interventions.

In relapsed or refractory (RR) metastatic germ cell cancer (GCC), high-dose (HD) chemotherapy (CTX) plus autologous stem cell transplantation is considered the standard of care. Limited data exist regarding the efficacy of HD-CTX following conventionally dosed salvage regimens (CDRs). This analysis explores and contrasts the efficacy of HD-CTX as the first or subsequent salvage regimen. Data were retrospectively collected to explore the efficacy of HD-CTX administered as the first (group A) or subsequent salvage CTX (group B) after a CDR. The primary endpoint was OS from the time of HD-CTX. Associations of survival, overall response rate (ORR), and toxicity with clinical characteristics were explored using stratified Kaplan-Meier and Cox regression models. Overall, 283 patients with GCC were included from 11 international centers, with 159 patients (56%) in group A and 124 patients (44%) in group B. The first salvage treatment was administered between 1998 and 2022, with a median follow-up of 27.0 [standard deviation (SD) 46.2] months for group A and 17.0 (SD 48.5) months for group B. The median OS from HD-CTX treatment initiation was not reached in group A, compared with 25 months in group B (P = 0.00027), associated with 2- and 5-year OS rates of 74% and 63% (group A) versus 53% and 37% (group B), respectively. When administered as the first salvage treatment, HD-CTX was associated with a higher ORR (79% versus 60%; P = 0.013) and lower nonhematologic grade ≥3 toxicity rate (78% versus 97%; P < 0.001). Concerning risk factor analysis for the total cohort, the International Prognostic Factors Study Group score was the only independent predictor of OS in multivariable analysis (P = 0.006). When administered as the initial salvage treatment or after CDR, HD-CTX exhibits curative potential for patients with RR GCC. The efficacy and safety outcomes were more favorable when HD-CTX was conducted as the first salvage treatment line.

The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.