Anne Greist

Cisplatin-based combination chemotherapy for disseminated germ cell tumors: long-term follow-up.

A retrospective analysis of the initial 229 cases of disseminated germ cell tumors treated at Indiana University with cisplatin, vinblastine, and bleomycin (PVB), with or without doxorubicin revealed 146 patients who are alive and disease-free with a minimum follow-up of 6 years and a median follow-up of 8.5 years. At 12 years, the estimated probability of survival is 65.0%, and the estimated probability of relapse-free survival for complete responders is 83.5%. Long-term complications, such as clinically significant organ toxicity or therapy-related second malignancies, have not been observed. The functional status of survivors is maintained, with 95% returning to their pretherapy status, of which 88% are fully employed. Of patients receiving chemotherapy without abdominal surgery, 35% have fathered healthy children posttherapy. Achievement of complete remission (CR) in disseminated germ cell tumors with cisplatin-based combination chemotherapy translates to long-term disease-free survival and cure for t...

Pathologic findings at orchiectomy following chemotherapy for disseminated testicular cancer.

Patients with testicular cancer who have disseminated disease at presentation do not always undergo orchiectomy for diagnosis of staging before initiation of chemotherapy. Between October 1978 and November 1982 orchiectomy was performed following cisplatin combination chemotherapy in 20 patients with disseminated germ cell tumors. There were three patients with residual carcinoma in the removed testis and six patients with teratoma. Therefore, in patients with evidence of a primary testicular neoplasm that was not resected initially, orchiectomy should be performed after chemotherapy. Furthermore, the testis may be a sanctuary site for germ cell malignancies during systemic treatment.

Prevalence and risk factors of cardiovascular disease (CVD) events among patients with haemophilia: experience of a single haemophilia treatment centre in the United States (US).

Summary.  The primary objective of the study was to examine the prevalence of cardiovascular disease (CVD) events and their known risk factors among persons with haemophilia (PWH). This cross‐sectional study, covering a 5‐year period, included PWH aged ≥35 years who were cared for at a single haemophilia treatment centre in the United States. Medical records were extensively reviewed to collect the information about CVD events and their risk factors such as obesity, hypertension, diabetes, hypercholesterolemia and smoking. Prevalence rates were compared with national population estimates and associations between risk factors and CVD events were examined using logistic regression. The study cohort comprised 185 PWH (102 haemophilia A and 83 haemophilia B). Lifetime prevalence of a CVD event was 19.5% (36/185, 95% confidence interval [CI] 13.8–25.2%). CVD mortality was 5.4% (10/185, 95% CI 2.7–8.1). Compared with US non‐Hispanic White males (NHWH), PWH had about twice the prevalence of coronary artery disease, stroke and myocardial infarction. The prevalence of CVD risk factors for PWH was similar to that for US NHWM with 39.5% of PWH exposed to two or more of these risk factors. Both hypertension and smoking were associated significantly with CVD events, with odds ratios of 4.9 and 6.3, respectively. In conclusion, this study revealed that both CVD events and its risk factors were at least equally prevalent among PWH and might have been even higher than among the US NHWM in the United States. Therefore, it is imperative to implement strategies for CVD prevention among PWH.

Central nervous system infections due to Stomatococcus mucilaginosus in immunocompromised hosts.

We present a case of central nervous system (CNS) infection due to Stomatococcus mucilaginosus involving a patient with leukemia and summarize 12 additional published reports of CNS infection due to this organism in immunocompromised hosts. The infection was diagnosed most commonly in the setting of hematologic malignancy accompanied by chemotherapy-induced neutropenia. S. mucilaginosus was recovered from blood prior to discovery of the CNS infection in 62% of cases. Signs or symptoms of CNS infection were observed in all patients. Although a number of patients responded to regimens containing intravenous vancomycin, the addition of intrathecal vancomycin appeared to be of benefit in some cases.

Variability in bleeding phenotype in Amish carriers of haemophilia B with the 31008 C-->T mutation.

Summary.  The aim of this study was to characterize the variability of bleeding phenotype and its association with plasma factor IX coagulant activity (FIX:C) in haemophilia B carriers in a large Amish pedigree with a unifying genetic mutation, C‐to‐T transition at base 31008 of the factor IX gene (Xq27.1–27.2). A cross‐sectional survey of haemophilia B carriers included a multiple choice questionnaire evaluating symptoms of mucocutaneous bleeding, joint bleeding and bleeding after haemostatic stress [menstruation, postpartum haemorrhage (PPH), dental extractions and invasive surgeries]. Severity of bleeding was graded as 0 to 4, 0 being no bleeding whereas 4 being severe bleeding. Association between total bleeding scores and the FIX:C was evaluated. Sixty‐four haemophilia B carriers participated in this study. Median age: 18 years (range 1–70 years); median bleeding score: 1 (range 0–8). Besides PPH, isolated symptoms of bruising, epistaxis, menorrhagia and postsurgical bleeding including dental extraction were not associated with lower FIX:C. Bleeding score ≥3 was associated with involvement of at least two bleeding sites and a lower mean FIX:C of 42 ± 10.3% (95% CI 36.4–47.7) while a score >3 had involvement of ≤2 sites and higher mean FIX:C of 54.9 ± 21.5% (95% CI 49–61), P = 0.005. Subcutaneous haematoma formation and bleeding after haemostatic stress requiring treatment were associated with bleeding scores ≥3. Phenotypic variability existed among the carriers of haemophilia B who belonged to a single pedigree carrying a single unifying mutation. The utility of bleeding scores to define bleeding phenotype precisely in haemophilia B carriers needs further evaluation.

Biologic response to subcutaneous and intranasal therapy with desmopressin in a large Amish kindred with Type 2M von Willebrand disease

Summary. The aim of this study was to characterize the adequacy and longevity of biological response to desmopressin (DDAVP) in a large Amish kindred of Type 2M von Willebrand disease (VWD) possessing C‐to‐T transition at nucleotide 4120 in exon 28 of A1 domain of von Willebrand factor (VWF) gene. Response to both intranasal (Stimate®) and subcutaneous DDAVP administration was assessed. Rise in ristocetin cofactor activity (VWF:RCo) ≥ 40% at 90‐min post‐Stimate® and 1–2 h after subcutaneous DDAVP was defined as initial response; response longevity was assessed only after subcutaneous dosing by measuring VWF:RCo levels at time‐points 1, 2, 4 and 6 h. Eleven patients (five males, six females; age range: 20–56 years) participated in intranasal and 9/11 (four males, five females) in subcutaneous testing. Baseline haemostatic profiles included: VWF:RCo < 15%, VWF:Ag < 40% and normal VWF multimers. Initial response was comparable by both intranasal (6/11; 54.5%) and subcutaneous (4/9; 44%) routes; sustained response (VWF:RCo > 40% for 2 h) was observed in only one in nine (11%) patients tested. Median VWF:RCo peak levels after intranasal (40%) and subcutaneous (39%) routes were equivalent. Peak VWF:Ag levels were significantly higher after subcutaneous than intranasal DDAVP (94% vs. 54%; P = 0.03). Area under the curve for VWF:RCo was significantly decreased (170 μg h mL−1) compared with VWF:Ag (471 μg h mL−1) and FVIII:C (624.60 μg h mL−1). This study suggests that in this population: (i) intra‐individual DDAVP response is consistent with subcutaneous and intranasal administration; and (ii) extending DDAVP challenge test up to at least 6 h is required to characterize adequacy and longevity of biologic response prior to using DDAVP as a sole haemostatic intervention.

Cisplatin-Based Combination Chemotherapy for Disseminated Germ Cell Tumors: Long-Term Follow-Up

A retrospective analysis of the initial 229 cases of disseminated germ cell tumors treated at Indiana University with cisplatin, vinblastine, and bleomycin (PVB), with or without doxorubicin revealed 146 patients who are alive and disease-free with a minimum follow-up of 6 years and a median follow-up of 8.5 years. At 12 years, the estimated probability of survival is 65.0%, and the estimated probability of relapse-free survival for complete responders is 83.5%. Long-term complications, such as clinically significant organ toxicity or therapy-related second malignancies, have not been observed. The functional status of survivors is maintained, with 95% returning to their pretherapy status, of which 88% are fully employed. Of patients receiving chemotherapy without abdominal surgery, 35% have fathered healthy children posttherapy. Achievement of complete remission (CR) in disseminated germ cell tumors with cisplatin-based combination chemotherapy translates to long-term disease-free survival and cure for the majority of patients, with preservation of functional status.