Case Report: Invasive Fungal Infection and Daratumumab: A Case Series and Review of Literature.

Life expectancy of multiple myeloma (MM) patients has improved in last years due to the advent of anti-CD38 monoclonal antibodies in combination with immunomodulators and proteasome inhibitors. However, morbidity and mortality related to infections remain high and represent a major concern. This paper describes the "real life" risk of invasive fungal infections (IFI) in patients treated with daratumumab-based therapy and reviews the relevant literature. In a series of 75 patients we only observed three cases of fungal pneumonia. Unfortunately, the early signs and symptoms were not specific for fungal infection. Diagnostic imaging, microbiology and patient history, especially previous therapies, are critical in the decision to start antifungal treatment. Recognising the subgroup of MM patients with high risk of IFI can increase the rate of diagnosis, adequate treatment and MM-treatment recovery.

Sirolimus-based graft-versus-host disease prophylaxis promotes the in vivo expansion of regulatory T cells and permits peripheral blood stem cell transplantation from haploidentical donors.

Hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA) haploidentical family donors is a promising therapeutic option for high-risk hematologic malignancies. Here we explored in 121 patients, mostly with advanced stage diseases, a sirolimus-based, calcineurin-inhibitor-free prophylaxis of graft-versus-host disease (GvHD) to allow the infusion of unmanipulated peripheral blood stem cell (PBSC) grafts from partially HLA-matched family donors (TrRaMM study, Eudract 2007-5477-54). Conditioning regimen was based on treosulfan and fludarabine, and GvHD prophylaxis on antithymocyte globulin Fresenius (ATG-F), rituximab and oral administration of sirolimus and mycophenolate. Neutrophil and platelet engraftment occurred in median at 17 and 19 days after HSCT, respectively, and full donor chimerism was documented in patients' bone marrow since the first post-transplant evaluation. T-cell immune reconstitution was rapid, and high frequencies of circulating functional T-regulatory cells (Treg) were documented during sirolimus prophylaxis. Incidence of acute GvHD grade II-IV was 35%, and occurrence and severity correlated negatively with Treg frequency. Chronic GvHD incidence was 47%. At 3 years after HSCT, transpant-related mortality was 31%, relapse incidence 48% and overall survival 25%. In conclusion, GvHD prophylaxis with sirolimus-mycophenolate-ATG-F-rituximab promotes a rapid immune reconstitution skewed toward Tregs, allowing the infusion of unmanipulated haploidentical PBSC grafts.

Unmasking of a Recessive SCARF2 Mutation by a 22q11.12 de novo Deletion in a Patient with Van den Ende-Gupta Syndrome.

Van den Ende-Gupta syndrome (VDEGS) is a congenital condition characterized by craniofacial and skeletal manifestations, specifically blepharophimosis, malar and maxillary hypoplasia, distinctive nose, arachnocamptodactyly, and long slender bones of the hands and feet. To date, only 24 patients have been described. It is generally thought that the syndrome is transmitted by an autosomal recessive mode of inheritance, although evidence for genetic heterogeneity has recently been presented. We report on a girl followed from birth up to 3 years of life with a set of peculiar minor anomalies, arachnocamptodactyly of hands and feet, characteristic of VDEGS in association with a 22q11.12 deletion. Recently, the VDEGS gene was mapped to the DiGeorge syndrome region on 22q11.2, and homozygous mutations in the SCARF2 gene were identified. We now report the first patient with VDEGS due to compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 splice site mutation.

Cryptic subtelomeric translocation t(2;16)(q37;q24) segregating in a family with unexplained stillbirths and a dysmorphic, slightly retarded child.

We here describe a submicroscopic translocation affecting the subtelomeric regions of chromosomes 2q and 16q, and segregating in a family with stillbirths, early pregnancy losses, and two dysmorphic and slightly retarded babies. FISH analysis showed a 46,XY,der(2)t(2;16)(q37.3;q24.3) in the propositus, and a balanced t(2;16) in his mother, her conceptus and maternal grandfather. FISH with YACs and BACs made it possible to map the 2q37 breakpoint precisely between the regions covered by y952E1 and y746H1, and the 16q breakpoint between the regions encompassed by bA 309g16 and bA 533d19. The contribution of 2q37.3 monosomy and 16q24.3 trisomy to the proband's phenotype is compared with that in reported patients with similar imbalances of either chromosome.

[Angiosarcoma of the breast after conservative surgery and radiotherapy for early breast carcinoma. Description of a case]. / L'angiosarcoma della mammella dopo chirurgia conservativa e radioterapia per carcinoma mammario precoce. Descrizione di un caso clinico.

The occurrence of an angiosarcoma of the residual breast after conservative surgery and adjuvant radiotherapy for early mammary carcinoma is a very rare event. In western countries only 57 cases have been published in the literature (5 in Italy) since the first described case in 1987. Radiotherapy seems to be the most important etiological factor in the development of the neoplasm. Diagnosis is often delayed, owing to the "benign" aspect of the lesion. The only effective treatment is residual mastectomy, because chemotherapy is ineffective. The prognosis is often dismal, because of the aggressive behaviour of the lesion in most cases. The case of a patient with a multicentric secondary angiosarcoma of the breast recently operated on is described.

Congenital cytomegalovirus infection in a northern Italian region. NEOCMV Group.

Knowledge of the prevalence of congenital cytomegalovirus infection is necessary to evaluate the need for prevention. We performed a multicentre one-year study involving 11 neonatology divisions to ascertain the prevalence in Lombardy. Cytomegalovirus was isolated by culturing saliva samples from all babies born (n = 1268) of two 15-day sample periods and from 185 neonates with suspected congenital CMV based on clinical and laboratory findings and the history. The overall prevalence of congenital infection was 0.47% (6/1268) in the sample period group and 5% (9/185) in the second group. Clinical monitoring revealed sequelae in two of three children with symptomatic infection and no asymptomatic child at age two years. In a subgroup of 205 babies including 14 of the infected infants we also evaluated a test to detect cytomegalovirus DNA in the Guthrie cards obtained in neonatal screening for genetic and metabolic disorders. The test's sensitivity was 100% and specificity 98.5%, encouraging its use for early identification of infected neonates and for large epidemiological studies.

[Traverso-Longmire technique and quality of life in patients operated on for periampullary neoplasms. Clinical contribution]. / Tecnica di Traverso-Longmire e qualità di vita nei pazienti operati per neoplasie periampollari. Contributo clinico.

BACKGROUND: The surgical approach to periampullary cancers represents one of the major components of digestive tract surgery. Personal experience in the treatment of 21 patients affected with periampullary neoplasms, operated on between January 1994 and July 1996 is reported. METHODS: Ten duodenopancreatectomies (DP) have been carried out (DP), 2 total pancreatectomies (TP). The remaining patients underwent palliative surgery: the resecability index was 57%. Primary cancer site included head of the pancreas in 10 cases, ampulla of Vater in 1 case and duodenum in 1 case. DP and TP have been performed using the pylorus-preserving technique, proposed by Traverso-Longmire. RESULTS: No operative mortality was reported; the morbidity rate was 25%. Nasogastric tube has been left in place for a mean time of 8 days (range 6-12). The mean postoperative period was 20 days (range 11-54). Five patients subsequently died for progressive disease: 4 during the first year (mean survival time 9 months), 1 during the second year (survival time 17 months). The follow-up of the remaining patients ranges between 6 and 30 months. Endoscopy, performed at 3-6-12 months, revealed no anastomotic recurrences, but 1 benign jejunal ulcer. CONCLUSIONS: According to personal experience the Traverso-Longmire technique is an effective procedure to improve the quality of life of these patients having a so poor expectancy of survival.

[Large retroperitoneal hemangiopericytoma. Presentation of a clinical case]. / Voluminoso emangiopericitoma retroperitoneale. Presentazione di un caso clinico.

Hemangiopericytoma is a rare and solitary solid tumor originating from pericytes, which are contractile pericapillary cells, first identified and described by Zimmermann in 1923. This neoplasm occurs most commonly in the lower extremities and retroperitoneum. The Authors describe the case of a patient affected with a giant retroperitoneal hemangiopericytoma. Echographic and computed tomographic scans have been fundamental in defining location and size of the neoplasm as well as its relations to the surrounding structures. However a definitive diagnosis was possible only by histologic examination, supported by the proper immunohistochemical stains. The Authors emphasize the difficulty to reliably predict the biological behaviour of these tumors and therefore the necessity of a follow-up of the patients for at least five years, even in the case of a histologically "benign" hemangiopericytoma.

[Cystic lymphangioma of the liver. Presentation of a clinical case]. / Il linfangioma cistico del fegato. Presentazione di un caso clinico.

The cystic lymphangioma of the liver is an extremely rare benign tumor that usually belongs to a systemic lymphangiomatosis. A case of an adult woman presenting a cystic lymphangioma as single hepatic lesion with no other viscera affected is described. Ultrasonography and computed tomography did not allow a differential diagnosis of the lesion from the more common hydatid cyst. Definitive diagnosis and treatment were reached only by exploratory laparotomy.