Clinical characteristics and outcome of patients over 60 years with Hodgkin lymphoma treated in Switzerland.

Hodgkin lymphoma (HL) in older patients appears to be a different disease compared with younger patients with historically lower survival rates. This is related to a variety of factors, including increased treatment-related toxicity, the presence of comorbidities, and biologic differences. In order to better assess the clinical characteristics, treatment strategies, and outcome of this particular population, we conducted a population-based, retrospective analysis including 269 patients with HL older than 60 years (median age 71 years, range 60-94), treated between 2000 and 2017 in 15 referral centers across Switzerland. Primary endpoints were overall survival (OS), progression-free survival (PFS), and cause-specific survival (CSS). The vast majority of patients were treated with curative intent, either with a combined modality approach (chemotherapy followed by radiation therapy) or with systemic therapy. At a median follow-up of 6.6 years (95% confidence interval [CI], 6.0-7.6), 5-year PFS was 52.2% (95% CI, 46.0-59.2), 5-year OS was 62.5% (95% CI, 56.4-69.2), and 5-year CSS was 85.1.8% (95% CI, 80.3-90.1) for the entire cohort. A significant difference in terms of CSS was observed for patients older than 71 years in comparison to patients aged 60-70 years (hazard ratio 2.6, 1.3-5.0, p = 0.005). Bleomycin-induced lung toxicity (BLT) was documented in 26 patients (17.7%) out of the 147 patients exposed to this compound and was more frequent in patients older than 71 years (15/60, 25%). Outcome of HL pts older than 71 years appeared to decrease substantially in comparison to the younger counterpart. Treatment-related toxicities appeared to be relevant, in particular, BLT. New, potentially less toxic strategies need to be investigated in prospective clinical trials in this particular frail population.

Multicentric Castleman's disease as a cause for unclear febrile episodes in a 55-year-old HIV-infected man.

Our case illustrates the difficulties involved in diagnosing multicentric Castleman's disease (MCD) in a human immunodeficiency virus-infected man with febrile episodes and malaise. In the absence of well-established treatment protocols, we have chosen a new treatment algorithm with rituximab, etoposide, and valganciclovir, which led to the remission of clinical symptoms. Yet, we advocate focused exploration for MCD in immunosuppressed patients with unclear febrile episodes, as recent advances in treatment are promising.

How useful is PET/CT imaging in the management of post-transplant lymphoproliferative disease after liver transplantation?

Post-transplant lymphoproliferative disease (PTLD) is a serious and potentially life-threatening complication after solid organ transplantation. Here, we report our first experience with the use of PET/CT (positron emission tomography combined with computed tomogram) for the management of patients with PTLD after liver transplantation. Four patients with histologically proven PTLD were analyzed. Conventional work-up included physical examination and head-to-pelvis CT. PET/CT was used in one patient for initial staging and in all patients for follow-up. PET/CT positive findings underwent biopsy. Information provided by PET/CT resulted in a change of medical management in three of the four patients. Conventional work-up missed residual disease after surgery in one and failed to detect a tumor relapse in another patient. However, one patient disclosed a false positive PET/CT finding in the lungs. In conclusion, PET/CT may be a useful tool for staging and therapy monitoring of PTLD after liver transplantation.

The SSX-2 gene, which is involved in the t(X;18) translocation of synovial sarcomas, codes for the human tumor antigen HOM-MEL-40.

Using autologous serum for the serological analysis of recombinantly expressed clones (SEREX) from a cDNA derived from a human melanoma, several new melanoma antigens were identified that are immunogenic in the autologous host. Sequence analysis revealed that one of these antigens, HOM-MEL-40, was coded for by the SSX2 gene, which has recently been described to be involved in the t(X;18) translocation of human synovial sarcomas. Expression analysis performed by Northern blot and RT-PCR demonstrated the presence of HOM-MEL-40 transcripts in a significant proportion of human melanomas (50%), colon cancers (25 %), hepatocarcinomas (30%), and breast carcinoma (20%) but not in normal tissues except for testis. Sequence comparison with transcripts cloned from testis ruled out mutations in the melanoma-derived HOM-MEL-40. Antibodies against HOM-MEL-40 were found in 10 of 89 patients with melanoma, including 3 of 8 patients with HOM-MEL-40-positive tumors, but not in 41 apparently healthy controls. In view of the specific expression pattern and immunogenicity in cancer patients, HOM-MEL-40 holds promise as a target for immune interventions in a considerable population of patients with HOM-MEL-40-positive tumors.

Human neoplasms elicit multiple specific immune responses in the autologous host.

Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with high-titer IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.

Autonomic dysfunction in patients with achalasia.

It has been previously shown that patients with achalasia may have motor abnormalities of the stomach, small bowel and biliary system. This study investigates whether a disturbance of extraintestinal autonomic function occurs. Autonomic function studies were performed in 15 patients with achalasia and 15 age- and sex-matched healthy controls. Pupillograms were obtained during darkness, light exposure and after pilocarpine administration. Cardiovascular function studies included determinations of heart rate variation during deep breathing and orthostasis. In addition, we determined blood pressure changes in response to sustained handgrip, cold exposure and orthostasis. Neurohormonal function was investigated by measuring serum pancreatic polypeptide (PP) levels prior to and following sham feeding. Pupillary function did not differ in patients as compared with controls. However, 9 of 15 patients (95% CI: 32-84%) and none of the controls showed at least one abnormal autonomic cardiovascular response. A significant difference between the two groups was observed in sympathetic function (P = 0.023). More patients than controls did not respond to sham feeding with a PP increase. It is concluded that some patients with achalasia exhibit an abnormality of the autonomic nervous system that extends beyond the gastrointestinal tract. These abnormalities mainly concern cardiovascular function but may also involve neurohormonal responses.