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Biomedical subjects

Giulio De Rossi

Publications and source records attributed to Giulio De Rossi.

16 recordsLinked to original sources
PubMed2006

Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience.

In idiopathic thrombocytopenic purpura (ITP), corticosteroids have been widely recognized as the most appropriate first-line treatment, even if the best therapeutic approach is still a matter of debate. Recently, a single high-dose dexamethasone (HD-DXM) course was administered as first-line therapy in adult patients with ITP. In this paper we show the results of 2 prospective pilot studies (monocentric and multicentric, respectively) concerning the use of repeated pulses of HD-DXM in untreated ITP patients. In the monocenter study, 37 patients with severe ITP, age at least 20 years and no more than 65 years, were enrolled. HD-DXM was given in 4-day pulses every 28 days, for 6 cycles. Response rate was 89.2%; relapse-free survival (RFS) was 90% at 15 months; long-term responses, lasting for a median time of 26 months (range 6-77 months) were 25 of 37 (67.6%). In the multicenter study, 95 patients with severe ITP, age at least 2 years and no more than 70 years, were enrolled. HD-DXM was given in 4-day pulses every 14 days, for 4 cycles; 90 patients completed 4 cycles. Response rate (85.6%) was similar in patients classified by age (<18 years, 36 of 42=85.7%; >or=18 years, 41 of 48=85.4%, P=not significant), with a statistically significant difference between the second and third cycle (75.8% vs 89%, P=.018). RFS at 15 months 81%; long-term responses, lasting for a median time of 8 months (range 4-24 months) were 67 of 90 (74.4%). In both studies, therapy was well tolerated. A schedule of 3 cycles of HD-DXM pulses will be compared with standard prednisone therapy (eg, 1 mg/kg per day) in the next randomized Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) trial.

Adolescent↗
PubMed2006

Idiopathic thrombocytopenic purpura (ITP) in children.

Idiopathic thrombocytopenic purpura in children remits spontaneously in the majority of cases but most children require treatment. Between 1995 and 2005, 265 children (0-15 years old) have been consecutively observed and treated: 28 children with high doses of methylprednisolone (HDMP) (15 mg/kgx4 days), 63 with HDMP (7.5 mg/kgx4 days), 37 with HD dexamethasone (DXM) pulses, 29 with low doses of MP, and 51 with different doses of intravenous immunoglobulins (IVIG) (0.4 or 0.8 g/kg). Fifty-seven children have not been treated because of a platelet count>or=10x10(9)/L and no significant bleeding. Two hundred forty-four (92.1%) children reached a persistent CR, 237 (89.4%) after a first-line treatment or the wait and see strategy. No statistically significant differences in CR related to different treatments have been observed. IVIG and HDMP (7.5 mg/kg for 4 days) are the best treatments to reach quickly safe platelet levels>or=30x10(9)/L (3-6 days) and CR (7-11 days). Among non-responding (NR) patients, seven have been splenectomized and three reached stable CR. These results emphasize differences with adult ITP.

Adolescent↗
PubMed2006

Osteogenesis induced by autologous bone marrow cells transplant in the pediatric skull.

BACKGROUND AND PURPOSE: The ability of cranial bone to repair defects of continuity is limited and it is mostly dependent on the age of the patient. In infancy and in early pediatric age, the scarce thickness of the calvarial bones and the need for a harmonic development of the child's skull limit the application of most of the surgical procedures usually utilized in older patients. We tested the ability of mononucleated cells, derived from the patient's bone marrow and transplanted on the site of the cranial bone defect, to increase the rate of mineralization of the autologous osteogenesis to obtain the complete restoration of the skull continuity. METHOD: Four children, aged 26, 28, 37, and 79 months, respectively, affected by a stabilized and persistent cranial bone defect of posttraumatic or postsurgical origin, were treated. A sandwich-shaped shell, made of extrused absorbable polylactic copolymers material, was used to hold in place a freeze-dried mineralized collagen matrix associated with a nonceramic hydroxyapatite scaffold, where autologous bone marrow mononucleated cells were inseminated. RESULTS: In all patients, a rapid autologous bone osteogenesis was observed with a clear dimensional reduction of the bone defect few months after the autologous bone marrow cells seeding. CONCLUSIONS: The preliminary results of this research suggest the use of autologous bone marrow cells to increase the autologous osteogenesis in early pediatric age in cases in which correction of skull bone defects is best realized with autologous bone.

Age Factors↗
PubMed2006

Role of treatment intensification in infants with acute lymphoblastic leukemia: results of two consecutive AIEOP studies.

Fifty-two infants with acute lymphoblastic leukemia (ALL) enrolled in the AIEOP ALL-91 and ALL-95 studies were treated with the intermediate or high risk protocols according to their presenting features and early response to treatment. The 5-year event-free survival was 33.3% (95% CI 12.1-54.5), 53.5% (95% CI 35.7-71.3) and 45.0% (95% CI 31.3-58.7) in the ALL-91 and ALL-95 studies and in the overall cohort, respectively. In the ALL-95 high-risk group (BFM therapy intensified by three blocks and double protocol II) nine of 17 patients treated with chemotherapy only and three of four transplanted patients were alive and in complete remission. The corresponding figures for patients treated in the ALL-91 high-risk protocol (reduced induction and nine blocks) were one of seven patients treated with chemotherapy only and none of two who were transplanted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Rapid T-cell receptor CD4+ repertoire reconstitution and immune recovery in unrelated umbilical cord blood transplanted pediatric leukemia patients.

Umbilical cord blood transplantation has been successfully employed for treatment of many immune and hematologic disorders. The aim of this study was to evaluate the quality of immune reconstitution after umbilical cord blood transplantation in 6 leukemia children. T-cell receptor Vbeta third complementary region spectratyping was used for monitoring the contribution of the thymic pathway in patients' immune reconstitution. Absolute numbers of lymphocyte subsets (T, B, and natural killer), and lymphoproliferative in vitro response to mitogens, recovered within 12 months after transplantation. Furthermore, an overall diversification of T-cell receptor complexity in the repopulating T cells, with a polyclonal Gaussian profiles in most (74%) of total families was observed. Noteworthy, we showed a wider and more rapid reconstitution of T-cell receptor CD4+ T cell families compared with T-cell receptor CD8+ T ones still exhibiting some perturbations at 24 months. These data show that umbilical cord blood transplantation allows immune reconstitution already within 12 months with generation of newly diversified CD4+ T lymphocyte subsets.

Adolescent↗
PubMed2006

Infant leukaemia: clinical, biological and therapeutic advances.

UNLABELLED: Infant acute lymphoid leukaemia (IALL) represents a distinct subset with an extremely poor response to therapy, despite major progress in the treatment of childhood leukaemia. However, several studies have shown that, even in this generally considered homogeneous group, a distinction could be made with regard to prognosis. The outcome of IALL patients with ALL-1/MLL rearrangements at the 11q23 cytogenetic band, early pre-B immunophenotype, high WBC count and age below 6 mo is significantly worse than in patients without these characteristics, and current therapies appear inadequate in a significant number of cases. Therefore, an international protocol (Interfant 99) was recently started, using a more aggressive approach, which included lymphoid- and myeloid-specific drugs, and indications for stem-cell transplantation. We reviewed the clinical characteristics of the disease, the results of several recent international clinical trials, and our experience with 16 infants with acute lymphoid leukaemia diagnosed and treated at our institution. CONCLUSION: It is extremely important to stratify patients for prognosis, taking into account clinical and biological variables with independent prognostic value. The aim is to select more adequate, risk-adapted, therapeutic strategies which also consider related or unrelated bone marrow transplant consolidation for patients with very poor prognosis.

Antineoplastic Agents↗
PubMed2005

Idiopathic hypereosinophilic syndrome: a case evolving in B-lymphoblastic lymphoma.

Idiopathic hypereosinophilic syndrome (HES) is a rare disease characterized by tissue involvement and organ dysfunction due to abnormal eosinophil proliferation. Evolution of HES into myeloid or T-cell malignancies has been frequently reported. Here, we describe a case of HES that preceded the occurrence of a high-grade B-lymphoblastic lymphoma in which clonal evolution has been demonstrated at the molecular level.

Humans↗
PubMed2005

GIMEMA-AIEOPAIDA protocol for the treatment of newly diagnosed acute promyelocytic leukemia (APL) in children.

The role of all-trans retinoic acid (ATRA) in pediatric acute promyelocytic leukemia (APL) is the topic of several ongoing studies. The results of the Italian pediatric experience with the multicentric Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA)-Italian Pediatric Hematology and Oncology Group (AIEOP) "AIDA" (ATRA and idarubicin) trial are presented. Of the 983 patients with APL enrolled in this protocol between January 1993 and June 2000, 124 (13%) had younger than 18 years. Treatment consisted of ATRA and idarubicin induction followed by 3 polychemotherapy consolidation courses. Molecular response by reverse transcriptase-polymerase chain reaction (RT-PCR) was assessed after consolidation and patients who were PCR- were randomized for different maintenances. One hundred and seven children were eligible and evaluable for induction: 103 (96%) achieved a hematologically complete remission. Overt ATRA syndrome was observed in 2 patients and pseudotumor cerebri was observed in 10 patients. Ninety-four patients were evaluable for RT-PCR analysis at the end of consolidation: 91 (97%) proved PCR+ and 3 PCR-. The overall survival and event-free survival (EFS) are 89% (95% confidence interval [c.i.]: 83%-95%) and 76% (c.i.: 65%-85%), respectively, at more than 10 years. A white blood cell (WBC) count at diagnosis of greater than 10 x 10(9)/L had a significant impact on EFS (59% vs 83% at 10 years). These results highlight the efficacy and feasibility of the AIDA protocol in the pediatric APL population.

Adolescent↗
PubMed2005

Treatment reduction in highly selected standard-risk childhood acute lymphoblastic leukemia. The AIEOP ALL-9501 study.

BACKGROUND AND OBJECTIVES: Treatment of childhood standard-risk (SR) acute lymphoblastic leukemia (ALL) is generally successful. However, intensive chemotherapy regimens may be associated with severe treatment sequelae. Efforts are therefore being made to identify those patients in whom less intensive treatment would be equally successful but cause fewer long-term sequelae. The aim of this study was to evaluate the efficacy of treatment reduction in a subset of children with ALL at minimal risk of failure. DESIGN AND METHODS: The population of patients with SR ALL included children aged between 1 and 6 years with less than 20,000 WBC/mm3, non-T immunophenotype, DNA index between 1.16 and 1.6, absence of t(9;22) and t(4;11) clonal translocations, no extramedullary leukemia, good response to prednisone and complete remission (CR) at the end of induction therapy. A reduced-intensity, BFM-type treatment schedule (AIEOP-ALL 9501 protocol) was used. Induction therapy was based on vincristine, prednisone, L-asparaginase and intrathecal methotrexate only; high-dose-methotrexate (2 g/m2) was given x4. The BFM Protocol II was given as reinduction therapy; thus the total dose of anthracyclines was 120 mg/m2 and no epipodophyllotoxins or cranial irradiation were employed. RESULTS: Between May 1995 and December 1999, 123 patients were identified as having SR-ALL (7.8% of the ALL-95 population), of whom 102 received the SR protocol. After a median follow-up of 5.9 years, 11 patients in the SR protocol had relapsed, 1 had died in remission, and 1 had developed a second malignant neoplasm. The probabilities (standard errors) of survival and event-free survival (EFS) were, respectively, 97.0% (1.7) and 86.7% (3.5) at 5 years, and 95.3% (2.4) and 86.7% (3.5) at 7 years. INTERPRETATION AND CONCLUSIONS: Although most of the relapsed patients were rescued, the long-term EFS probability in this small, highly selected group of patients remains inferior to expectation. Thus, alternative selection criteria, such as treatment response measured by minimal residual disease, should be considered to address the issue of treatment reduction.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Outcome of very late relapse in children with acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: Few data are available on the long-term outcome of children who present with a very late relapse of acute lymphoblastic leukemia, so treatment of these patients remains controversial. The present study was aimed at investigating clinical features and treatment outcome of children with very late relapse, diagnosed and treated in Italy in the last 20 years. DESIGN AND METHODS: All children diagnosed in Italian centers with a first relapse of acute lymphoblastic leukemia occurring >or= 60 months after attainment of first complete remission were included in this study. These relapses were diagnosed between 1982 and 1997. RESULTS: Ninety-three patients (58 males, 62.4%) had a first very late relapse occurring at a median time of 6.1 years (range 5.8 - 13.7 years) after the initial diagnosis. At a median follow-up time of 9.1 years after relapse, the overall 5-year survival (SE) and event-free-survival (SE) were 55.6% (5.2) and 39.5% (5.1), respectively. In multivariate analysis the site of relapse was the only significant predictor of duration of the second complete remission. Patients with isolated bone marrow relapse fared worse than those with combined or isolated extramedullary relapse [5-year event-free survival (SE) 24.5% (5.9), 51.3% (11.1) and 68.4% (10.7), respectively; (p=0.004)]. All 7 patients who underwent an allogeneic bone marrow transplantation from a matched related donor are alive in second complete remission. INTERPRETATION AND CONCLUSIONS: In this evaluation patients with a very late relapse isolated to the bone marrow had a poor outcome while re-treatment of extramedullary or combined relapse was associated with better cure rate. Our data suggest that patients with very late isolated bone marrow relapse should be treated intensively; bone marrow transplantation from a matched related donor may be indicated.

Adolescent↗
PubMed2003

Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis.

Autosomal-recessive osteopetrosis is a severe genetic disease caused by osteoclast failure. Approximately 50% of the patients harbor mutations of the ATP6i gene, encoding for the osteoclast-specific a3 subunit of V-ATPase. We found inactivating ATP6i mutations in four patients, and three of these were novel. Patients shared macrocephaly, growth retardation and optic nerve alteration, osteosclerotic and endobone patterns, and high alkaline phosphatase and parathyroid hormone levels. Bone biopsies revealed primary spongiosa lined with active osteoblasts and high numbers of tartrate-resistant acid phosphatase (TRAP)-positive, a3 subunit-negative, morphologically unremarkable osteoclasts, some of which located in shallow Howship lacunae. Scarce hematopoietic cells and abundant fibrous tissue containing TRAP-positive putative osteoclast precursors were noted. In vitro osteoclasts were a3-negative, morphologically normal, with prominent clear zones and actin rings, and TRAP activity more elevated than in control patients. Podosomes, alphaVbeta3 receptor, c-Src, and PYK2 were unremarkable. Consistent with the finding in the bone biopsies, these cells excavated pits faintly stained with toluidine blue, indicating inefficient bone resorption. Bone marrow transplantation was successful in all patients, and posttransplant osteoclasts showed rescue of a3 subunit immunoreactivity.

Acid Phosphatase↗
PubMed2003

A multiplex reverse transcriptase-polymerase chain reaction strategy for the diagnostic molecular screening of chimeric genes: a clinical evaluation on 170 patients with acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: In the last few years molecular methods have allowed the identification of leukemia-associated genetic lesions, which may represent the most accurate predictors of clinical outcome. These considerations strengthen the need for rapid identification of the abnormalities. Our aim was to demonstrate whether a modified multiplex reverse transcription polymerase chain reaction (RT-PCR) system might be successfully used to screen a large number of patients with acute lymphoblastic leukemia (ALL). DESIGN AND METHODS: In this study we adapted the multiplex RT-PCR assay, previously described by Pallisgaard et al., to detect all the most frequent genetic lesions with their characteristic splicing variants occurring in acute lymphoblastic leukemia, such as the MLL/AF4, MLL/ENL, BCR/ABL p190 (e1a2) and p210 (b2a2,b3a2) isoforms, E2A/PBX1, TEL/AML1, SIL/TAL1 and the novel NUP98/RAP1GDS1 transcript, recently described in a T-ALL leukemic subtype. RESULTS: We used the multiplex RT-PCR assay to screen 170 ALL patients (70 children and 100 adults). PCR positivity was detected in 67 (39%) of the 170 ALL patients studied. The comparison between cytogenetic and molecular analyses showed complete correspondence between the two assays in all patients with an evaluable karyotype. Finally, the observed incidence of genetic lesions in our ALL patients was similar to the frequency usually reported both in children and in adults with ALL. INTERPRETATION AND CONCLUSIONS: These results show that, compared to single RT-PCR reactions, our multiplex RT-PCR system allows rapid, specific, simultaneous as well as a less expensive, laborious and time-consuming detection of the most frequent fusion transcripts in ALL patients. Therefore, it might be recommended for rapid diagnostic molecular screening of large numbers of patients, such as those enrolled in multicenter, co-operative studies. Furthermore, we have shown that multiplex RT-PCR is an open system that can easily be adapted to detect new leukemic genes.

Adult↗
PubMed2003

Osteonecrosis: An emerging complication of intensive chemotherapy for childhood acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: Osteonecrosis (ON) is a potentially disabling complication of combination chemotherapy including high doses of steroids. The incidence and main risk factors for symptomatic ON have been investigated in a large group of children treated with high-dose steroids, prednisone and dexamethasone for childhood acute lymphoblastic leukemia (ALL). DESIGN AND METHODS: From May 1995 to December 1999, 1421 patients <18 years old, with newly diagnosed non-B ALL, were registered in the AIEOP-ALL 95 study. Their data were reviewed to identify patients who developed symptomatic ON. For those who were positively identified additional data were requested concerning ON-related symptoms, treatment and outcome. RESULTS: Overall, 15 of the 1421 patients developed symptomatic ON (1.1%) in a total of 29 sites. The estimated 5-year cumulative risk for clinically diagnosed ON was 1.6% (SE 0.4). The incidence was significantly higher among females (p=0.01) and older patients, with a peak rate of 7.4% (2.3) among those aged 10 to 17 years (p<0.0001). When the two factors, i.e. age and gender were combined, there was a striking increase in the risk among female patients aged 10 to 17 years. The median time between the diagnosis of ALL and that of ON was 17 months (range 8-45). The hip was the most frequently involved (19/29) site. INTERPRETATION AND CONCLUSIONS: Symptomatic ON occurred in only 1.1% of patients treated with BFM-type, intensive chemotherapy for childhood ALL. Female adolescents appear to be the subset of patients with the highest risk of ON, especially when categorized as having high risk leukemia and thus administered higher cumulative doses of dexamethasone.

Adolescent↗
PubMed2002

Improved outcome in high-risk childhood acute lymphoblastic leukemia defined by prednisone-poor response treated with double Berlin-Frankfurt-Muenster protocol II.

One hundred ninety-eight children and adolescents were entered in the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP)-ALL95 study for high-risk acute lymphoblastic leukemia (ALL). Inclusion criteria were poor response to initial prednisone/intrathecal methotrexate (prednisone-poor response [PPR]), resistance to induction therapy, translocation t(9;22), infants with the t(4;11), or CD10(-) ALL. The event-free survival (EFS) rate at 4 years was 56.5% (SE, 3.9%) for the entire group. The overall EFS rate in the current study was significantly better (P =.002) than that obtained in a comparable group of patients treated in the early 1990s in the AIEOP-ALL91 study. In particular, patients with PPR had a 4-year EFS of 61.1% (SE, 4.4%) versus 42.8% (SE, 5.4%) in the ALL 91 study (P =.008). Among PPR patients, those who were PPR-only (60.1%)-that is, they achieved CR and were negative for t(9;22) and t(4;11) translocations-had the best outcomes with this intensive treatment, even when additional adverse features (hyperleukocytosis, T phenotype) were present (4-year EFS, 70.1%; SE, 4.7%). We attribute this improvement to the replacement of 6 alternating blocks of non-cross-resistant drugs with an 8-drug reinduction regimen (Berlin-Frankfurt-Muenster [BFM] protocol II), repeated twice, in the context of a standard BFM-type intensive chemotherapy for high-risk ALL. This modified therapy may lead to high cure rates for patients defined as at high risk for intrinsic resistance to corticosteroids only.

Adolescent↗
PubMed2002

Allogeneic bone marrow transplantation for infantile globoid-cell leukodystrophy (Krabbe's disease).

A 4-month-old-girl affected by early expression of Krabbe's disease was treated with allogeneic bone marrow transplantation (BMT). The stem cell donor was her heterozygous HLA-identical mother. The central nervous system (CNS) involvement at diagnosis was evident, but minimal. After BMT the child presented a severe hypotonia and an acute tetraventricular hydrocephalus; she died 180 days after the BMT with progressive severe neurologic deterioration. Leukocyte galactocerebrosidase (GALC) activity was present at donor levels 20 days after BMT. Full donor chimerism was evident 18 days after BMT. This report confirms that in early onset "Krabbe's syndrome" if the diagnosis is delayed after the birth, the progression of the neurologic deterioration is not reversed by BMT. It is to be demonstrated if a very early hemopoietic stem cell transplantation during the first weeks of life, could be appropriate and efficacious.

Age of Onset↗