Giovanna Palumbo

Marriage and parenthood among childhood cancer survivors: a report from the Italian AIEOP Off-Therapy Registry

Background The aim of this study was to describe the patterns of marriage and parenthood in a cohort of childhood cancer survivors included in the Off-Therapy Registry maintained by the Italian Association of Pediatric Hematology and Oncology. Design and Methods We analyzed a cohort of 6,044 patients diagnosed with cancer between 1960 and 1998, while aged 0 to 14 years and who were 18 years old or older by December 2003. They were followed up through the regional vital statistics registers until death or the end of follow up (October 30, 2006), whichever occurred first, and their marital status and date of birth of their children were recorded. The cumulative probabilities of being married and having a first child were computed by gender and compared by tumor type within the cohort. Marriage and fertility rates (the latter defined as the number of live births per woman-year) were compared with those of the Italian population of the same age, gender, area of residence and calendar period by means of the observed to expected (O/E) ratios. Results During the follow-up period, 4,633 (77%) subjects had not married. The marriage O/E ratios were 0.56 (95% CI: 0.51–0.61) and 0.70 (95% CI: 0.65–0.76) among men and women, respectively. Overall, 263 men had 367 liveborn children, and 473 women had 697 liveborn children. The female fertility O/E ratio was 0.57 (95% CI: 0.53–0.62) overall, and 1.08 (95% CI: 0.99–1.17) when analyses were restricted to married/cohabiting women Conclusions Childhood cancer survivors are less likely to marry and to have children than the general population, confirming the life-long impact of their previous disease on their social behavior and choices. The inclusion of counseling in the strategies of management and long-term surveillance of childhood cancer patients could be beneficial to survivors as they approach adulthood.

Thrombocythemia and polycythemia in patients younger than 20 years at diagnosis: clinical and biologic features, treatment, and long-term outcome

Sixty-four patients < 20 years of age, investigated for a suspicion of Philadelphia-negative myeloproliferative disease (MPD), were retrospectively evaluated to characterize the different forms and to examine the treatments used and long-term outcome. JAK2 mutations, endogenous erythroid colony growth, and clonality were investigated in 51 children. Mutations of thrombopoietin, the thrombopoietin receptor (MPL), and the erythropoietin receptor and mutations of other genes involved in the pathogenesis of MPD were investigated in JAK2 wild-type patients. Based on our criteria for childhood MPD, we identified 34 patients with sporadic thrombocythemia (ST), 16 with hereditary thrombocytosis (HT), 11 with sporadic polycythemia (SP), and 3 with hereditary polycythemia (HP). JAK2(V617F) mutations were present in 47.5% of ST and in no HT. The MPL(S505A) mutation was detected in 15/16 HT patients and in no ST (P < .00001). The JAK2(V617F) mutation occurred in 27% of SP patients diagnosed according to the Polycythemia Vera Study Group or World Health Organization 2001 criteria. Children with ST received more cytoreductive drugs than those with HT (P = .0006). After a median follow-up of 124 months, no patient had developed leukemia or myelofibrosis and 5% had thrombosis; the miscarriage rate in thrombocythemic patients was 14%. The low complication rate in our population suggests that children with MPD may be managed by tailored approaches.

High levels of antiphospholipid antibodies are associated with cytomegalovirus infection in unrelated bone marrow and cord blood allogeneic stem cell transplantation

Antiphospholipid antibodies (APA) are a family of autoimmune and alloimmune immunoglobulins recognizing protein–phospholipid complexes in in vitro laboratory test systems. These antibodies have been associated with several conditions (malignancies, autoimmune diseases, infections, use of drugs); moreover, a syndrome capable of inducing thromboembolic disease has recently been associated with the presence of these antibodies. The aim of this prospective study was to investigate the levels of APA in subjects affected by haematological malignancies undergoing allogeneic haematopoietic stem cell transplantation (ASCT). Between March 1996 and December 1997, 32 patients undergoing ASCT were studied prospectively until day +180 from transplant. The mean values of IgG and IgM anticardiolipin antibodies (ACA) increased in recipients of stem cells from anunrelated donor, and a statistically significant difference inACA IgG mean value between unrelated and related transplanted patients was demonstrated between days +95 and +180. All of the subjects who received stem cells from an unrelated donor had APA levels higher than the mean normal value +3 SD vs. 35% of those receiving stem cells from a related donor (P < 0·01). The reason for such a difference may be a result of the different incidence in documented cytomegalovirus (CMV) infection in the two groups (83% vs. 23%; P < 0·01), as indicated by the significant correlation between APA positivity and CMV infection (P < 0·05). No relationship was found between APA, conditioning regimen and acute or chronic graft vs. host disease (GVHD). Moreover, we did not observe any thromboembolic disorder or veno occlusive disease (VOD).

Thalidomide does not modify the prognosis of plasma cell leukemia patients: Experience of a single center

Plasma cell leukemia (PCL) represents the most advanced stage of multiple myeloma (MM) with the neoplastic cells circulating in the peripheral blood. Its diagnosis requires an absolute peripheral blood plasma cell count of 426 10/l or 420% of the differential white blood cell count [1]. PCL is classified into two clinical types: the primary type occurs in individuals without being preceded by MM, whereas the secondary one is a rare complication of the late-stage MM. Based on observations that in PCL the response to standard therapy is extremely poor and the use of Thalidomide (Thal) in advanced myeloma has resulted in marked responses even in patients with advanced diseases, including those who relapsed after high-dose chemotherapy [2], we decided to use this promising drug also in patients with PCL. According to the schedule reported by Singhal et al. [2], between March 2000 and July 2002, after written informed consent, five PCL (two primary and three secondary) patients were considered eligible for Thal treatment at our Institution. Thal was administered as single agent, according to a compassionate-use protocol. The starting dose of Thal was 100 mg daily for 2 weeks; subsequently, this dosage was increased by 100 mg every other week, to a maximum of 600 mg per day or according to the maximum tolerated dose. According to the International Stage criteria, two patients were in stage III (b2 microglobulin 45.5 mg/dl) and three in stage II (one for a b2 microglobulin of 4.2 mg/dl and two for serum albumin levels of 2.4 and 2.9 g/dl, respectively). No cytogenetics, labeling index or FISH data are available for these patients. Three were males and two females; median age was 68 years (range 51 – 72). Two cases were IgG, 1 IgA and two expressed light chains; one patient had serum creatinine 42 mg/dl. With regard to disease status, three patients (two primary and one secondary PCL) were refractory (defined as progression while on therapy) to prior chemotherapies and two were in relapse. All had been treated with at least two lines of treatment, including high-dose induction therapy for one of them, and were included in this study after 14 months (range 8 – 41) of median follow-up. All patients received Thal for at least 1 month and were, therefore, evaluable for response. No patient responded, although a reduction of circulating PC was observed in two. Survival was very short, all patients died after 40, 45, 60, 75 and 120 days of Thal treatment, respectively. During the same time period we treated with the same protocol 75 MM patients (33 refractory to prior chemotherapies and 42 in relapse). The median age was 63.5 years (range 33 – 84); 47 patients were IgG, 20 IgA and eight had light chain MM. Highdose induction therapy was utilized for 29 of them and the MM patients were included in this study after 36 months of median follow-up from diagnosis. The median daily dose of Thal administered to all patients was 400 mg (range 100 – 600 mg). Among the 75 MM patients, 67 received Thal for at least 1 month and were evaluable for response; the remaining eight patients were not evaluable because four

Intermediate-dose cyclophosphamide and granulocyte colony-stimulating factor is a valid alternative to high-dose cyclophosphamide for mobilizing peripheral blood CD34+ cells in patients with multiple myeloma

Peripheral blood stem cells (PBSC) are widely used in the setting of dose-intensive chemotherapies in patients with multiple myeloma (MM). Although the granulocyte colony-stimulating factor (G-CSF), following chemotherapy or not, is considered the standard growth factor for mobilizing PBSC, the optimal chemotherapeutic regimen still remains to be defined. Cyclophosphamide (CTX) is an effective drug in the treatment of MM which is capable of mobilizing PBSC if followed by growth factors, even though administration of high-dose CTX (7 g/m2) results in severe toxicity requiring hospitalization and increasing costs. We have retrospectively analyzed the results obtained in 38 newly diagnosed MM patients treated with 1.2 g/m2 CTX on days 1 and 3 combined with 40 mg dexamethasone daily for 4 days. The results were compared with those obtained in 25 newly diagnosed MM patients treated with 7 g/m2 CTX. A higher number of CD34+ cells/kg was collected during the first leukapheresis and a statistically significant lower consumption of G-CSF was observed following two doses of 1.2 g/m2 CTX compared to the 7 g/m2 CTX dose. The possibility of treating patients with day-hospital regimens, with a satisfactory yield of hematopoietic cells harvested, may have relevant economic implications for treatment strategies in MM patients.

As compared to kaolin clotting time, silica clotting time is a specific and sensitive automated method for detecting lupus anticoagulant

Lupus anticoagulants (LAs) are antiphospholipid antibodies capable of interfering with the coagulation system and modifying in vitro the phospholipid-dependent clotting tests. Colloidal silica was used as activator to perform an activated partial thromboplastin time (aPTT) in 73 plasma samples with pathologically elevated kaolin clotting time (KCT) values using a photooptical automated coagulometer. Samples were incubated for 5 min with micronized silica, and after recalcification, the clotting times were measured. Pathologically prolonged results were confirmed by a confirmation and a neutralization test adding platelet-poor normal plasma (PPNP) and natural phospholipids, respectively. Silica clotting time (SCT) was abnormally elevated in 72/73 (98.6%) (mean ratio 1.71 +/- 0.28) KCT positive samples and normalized (mean ratio 1.03 +/- 0.16) after adding natural phospholipids to test plasma. The values expressed as SCT and KCT ratios were significantly correlated (r = .92; P < .001). SCT was normal in 40 healthy subjects utilised as controls (mean ratio 0.99 +/- 12). Sensitivity, specificity and diagnostic accuracy of SCT were 98.6%, 100% and 97.6%, respectively. Our data suggest that SCT is a sensitive test for detecting LA with a prolonged KCT in automated photooptical coagulometers. This peculiarity makes it particularly useful, in combination with diluted Russel viper venom time (dRVVT), for large-scale screening tests on LA.

CALR mutations in patients with essential thrombocythemia diagnosed in childhood and adolescence

To the editor: After the recent discovery of various mutations of the CALR gene, <10% of adult patients with essential thrombocythemia (ET) or primary myelofibrosis carry no identified molecular markers.[1][1],[2][2] More rarely, ET may occur also in children and adolescents.[3][3] We evaluated, by

Platelet function and coagulation abnormalities in type 1 Gaucher disease patients: effects of enzyme replacement therapy (ERT)

All individuals or their parents gave informed consent to the study. Laboratory tests were performed at initial diagnosis and, at planned intervals, during ERT. Platelet counts were done with the Advia 120 Bayer instrument (Swords Co., Dublin, Ireland); bleeding time was tested using a fully automated incision; prothrombin time (PT), activated partial thromboplastin time (APTT) tests and fibrinogen were measured using routine laboratory technique. Results were expressed as the ratio of times in seconds of test plasma and reference normal plasma (normal PT ratio: 0.90–1.14; normal APTT ratio: 0.92–1.16). Coagulation factor activities were

Gamma-delta hepatosplenic T-cell lymphoma. Description of a case with immunophenotypic and molecular follow-up successfully treated with chemotherapy alone

This study hereby reports the case of a 19-year old boy with a gamma-delta hepatosplenic T-cell lymphoma (HSTCL). Initial therapy consisted of four cycles of the IEV (Ifosphamide, Epirubicin and Etoposide) scheme. Further treatment strategy was then adapted according to minimal residual disease monitoring by immunophenotypic and T-cell receptor gamma chain gene evaluation. The patient remains in complete clinical, immunological and molecular remission and in good clinical conditions 48 months after diagnosis and 40 months after stopping therapy.

CODOX-M/IVAC (NCI 89-C-41) in children and adolescents with Burkitt's leukemia/lymphoma and large B-cell lymphomas: A 15-year monocentric experience

During the last 15 years, we have used the National Cancer Institute (NCI) 89-C-41 protocol in patients aged younger than 21 years with Burkitts leukemia/lymphoma (BLL) and diffuse large B-cell lymphoma (DLBCL). According to the Magrath staging system, patients were classified as low and high risk. Low-risk received three cycles of the CODOX-M regimen; high-risk patients received four alternating cycles with the CODOX-M and IVAC regimens. Thirty-five patients entered the study: 32 (91%) achieved complete remission (CR); three were non-responders and died and one patient died in CR. Two responders relapsed after 2 months and one presented early B acute lymphoblastic leukemia 33 months from the end of therapy. The 5-year overall survival and event free-survival are 83% and 80%, respectively. No late toxicity was registered. In our experience with a median follow-up of 11 years, the NCI 89-C-41 protocol has confirmed its high cure rate in BLL and DLBCL children and adolescents.