Thirty-seven adult patients with acute lymphoblastic leukemia were treated with a protocol called HEAV'D including Adriamycin, Vincristine, L-Asparaginase, Cyclophosphamide and Dexamethasone. The complete remission rate was 70 per cent. The median duration of remission was more than 30 months. Patients with initial leukocyte count below 20 000/mmc experienced a longer remission (median not reached) than patients with a leukocyte count above 20 000/mmc (median 10 months).

Adolescent↗

PubMedDate not supplied

Short-term remission induction and consolidation therapy for adult acute myelogenous leukemia.

One hundred and ninety two adults (median age 44 years) with de novo or secondary (n = 17) acute myelogenous leukemia (AML) were managed with a maximum of six intended courses with adriamycin 25 mg/m2/d for three days, plus cytarabine 200 mg/m2/d and 6-thioguanine 200 mg/m2/d for seven days (short-term therapy, STT). Twenty eight patients not in remission after the first course were given cytarabine 2 g/m2/bd for six days, a treatment that was highly toxic and gave a low CR rate. One hundred and twenty-six patients overall (66 per cent) achieved a complete remission (CR), 117/164 (71 per cent) after one to three standard courses (median 1), and 9/28 (32 per cent) after high-dose cytarabine. Median CR duration was 12 months. By multivariate analysis, younger age, blast count less than or equal to 50 x 10(9)/L, and de novo AML were associated with a better outcome (p less than 0.05). CR duration correlated favourably with FAB M3 morphology and total number (five or six) of cycles (p less than 0.05). In patients receiving five or six total courses, median CR length resulted 15.5 months and leukemia-free survival at 3 years 37 per cent. Therapy was curtailed in one fourth of CR patients because of unacceptable toxicity, and there were nine early deaths attributable to therapy-related complications among 126 CR cases. STT may be a worthwhile form of treatment for patients with de novo non-hyperleukocytic AML that are able to tolerate five or six consecutive induction-like chemotherapy courses.

Adolescent↗

PubMedDate not supplied

Intensive retreatment of adults and children with acute lymphoblastic leukemia.

Twenty-three patients (16 adults) failing their first or subsequent (n = 8) intensive treatment for de novo acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia lymphoid blast phase (n = 2) were managed with protocol POG 8201, originally introduced in relapsed ALL of childhood. In this programme, a four-drug induction phase is followed by early consolidation with teniposide-cytarabine, intrathecal chemotherapy, continuation weekly chemotherapy alternating teniposide-cytarabine with vincristine-cyclophosphamide, and periodic reinduction courses. Fourteen adults and five children with ALL achieved a complete response (CR) (86 per cent). The highest response rate (100 per cent) was obtained in 12 patients treated at first relapse after an initial CR of greater than 18 months (p = 0.07). Median duration of CR was 8 months in adults and 11 months in children. A longer than previous one CR (inversion) was obtained in four cases. Four ALL patients were successfully transplanted from a matched sibling after 3-11 months from achievement of CR. Median overall survival in adults with ALL was 11 months, significantly longer than for 40 comparable cases treated intensively but without rotational continuation therapy in previous years (p less than 0.001). This regimen is applicable to adults with relapsed ALL, where prolongation of survival may allow time for effective salvage with bone marrow transplantation.

Adolescent↗

PubMedDate not supplied

Reinforced HEAV'D therapy for adult acute lymphoblastic leukemia: improved results and revised prognostic criteria.

Thirty-six adults with acute lymphoblastic leukemia (ALL) were treated with adriamycin, vincristine, prednisolone, and asparaginase for remission induction, followed by vincristine-adriamycin-cyclophosphamide consolidation courses, cranial irradiation, a short ara-C plus VM-26 pulse, and vincristine plus cyclophosphamide rotating weekly with ara-C plus VM-26 for three months (reinforced HEAV'D). Thirty-one patients achieved a complete remission (86 per cent). Compared with historical results from a prior study, age > 30 years, absolute blast count > 15 x 10(9)/l, and CD10-negative immunophenotype were not associated with higher relapse rate and shorter survival, suggesting a positive effect from intensification therapy with ara-C and VM-26 in these poor prognostic categories. However, patients with an abnormal karyotypic pattern or a positive molecular study for BCR-ABL rearrangement detecting t(9;22) had a far greater likelihood of treatment failure (probability of remission at 3 years 0.10) than those with normal karyotype or negative molecular study (probability 0.70), and those not studied or with insufficient methaphases (probability 0.50) (p < 0.05 by log-rank test). These results underline the prognostic importance of chromosomal abnormalities and the usefulness of ara-C and VM-26 in the management of adult ALL.

Adolescent↗

PubMedDate not supplied

Diagnostic and prognostic significance of platelet-bound IgG measurement in immune thrombocytopenic purpura.

The test proposed by Dixon et al. is an important contribution to the technique for detection of platelet-associated antibody. This test measures platelet-associated IgG by a complement-mediated red blood cell lysis-inhibition technique. We have used the direct Dixon test to study 44 cases of immune thrombocytopenic purpura and 90 controls, including subjects with nonimmune thrombocytopenic purpura and healthy subjects. Increased PAIgG was noted in 86.3% of ITP patients. However, the pretreatment values of PAIgG were not helpful for predicting the therapeutic response to either prednisone or splenectomy. Six patients in long-term clinical remission had normal platelet counts and distinctly abnormal PAIgG values. This condition was associated with qualitative platelet functional defects. This latter finding seems to be of diagnostic interest and deserves further investigations.

Adolescent↗

PubMedDate not supplied

Synthesis and characterization of cross-linked chitosan microspheres for drug delivery applications.

The present study deals with the synthesis and characterization of cross-linked chitosan microspheres containing an hydrophilic drug, hydroquinone. The microspheres were prepared by the suspension cross-linking method using glutaraldehyde as the cross-linking agent of the polymer matrix. Perfectly spherical cross-linked hydrogel microspheres loaded with hydroquinone were obtained in the size range of 20-100 microm. The effect of the degree of polymer cross-linking, chitosan molecular weight, chitosan concentration and amount of the encapsulated drug on the hydroquinone release kinetics was extensively investigated. It was found that slower drug release rates were obtained from microspheres prepared by using a higher initial concentration of chitosan, a higher molecular weight of chitosan or/and a lower drug concentration. Most importantly, it was shown that the release rate of hydroquinone was mainly controlled by the polymer cross-linking density and, thus, by the degree of swelling of the hydrogel matrix.

Chitin↗

PubMedDate not supplied

A follow-up study of 49 adult patients with idiopathic thrombocytopenic purpura treated with high-dose immunoglobulins and anti-D immunoglobulins.

BACKGROUND: We analyze here short- and long-term results in 49 patients with idiopathic thrombocytopenic purpura (ITP), consecutively treated with high-dose (h.d.) immunoglobulins (Ig) or anti-D Ig. The major aims of this study were to assess the prognostic power of some patient characteristics and to verify the possibility that repeated courses of treatment can induce a stable remission. Moreover, the relative efficacy and safety of these two treatments were compared. PATIENTS AND METHODS: Group A included 28 patients with chronic ITP and 17 with ITP of recent onset who were receiving h.d. Ig; Group B included 5 patients with ITP of recent onset and 7 with chronic ITP treated with anti-D Ig. Eight cases, receiving both treatment, were included in both groups. Response to treatment was defined as any increase in platelet count above 30 x 10(9)/l, when the platelet count was less than 10 x 10(9)/l, or any doubling of the basal platelet count otherwise. Remission was defined as any platelet count higher than 100 x 10(9)/l lasting for 3 months or longer without therapy. RESULTS AND CONCLUSIONS: Cumulative response and remission rate was not statistically different in the two groups. Multivariate logistic regression analysis showed no influence of sex, previous therapy or duration of disease. Patients older than 60 years were definitely less responsive to h.d. Ig (58% vs 92%, p = 0.03). In Group A, two patients obtained remission after the first course of h.d. Ig. No additional remissions were obtained by repeated courses of h.d. Ig, apart from a single case of ITP of recent onset.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Fulminant sepsis in adults splenectomized for idiopathic thrombocytopenic purpura.

BACKGROUND AND METHODS: Splenectomy is still a mainstay in the treatment of idiopathic thrombocytopenic purpura (ITP). Although the risk of fulminant sepsis after splenectomy in children and in adults has been known for a long time, the true prevalence of fulminant sepsis in adults splenectomized for ITP has still not been well established, despite many anecdotal reports. In this paper we have tried to estimate this risk by reviewing the available literature and by analyzing a large cohort of adults splenectomized for ITP at our Institute since 1970. RESULTS: Two cases of fulminant sepsis (a 21-year-old man and a 24-year-old woman) were traced in a group of 133 splenectomized adults, with a crude incidence of 1.5% or, equivalently, of 0.17 cases per 100 patient-years. No case of sepsis occurred in a control group of 323 non splenectomized ITP adults. This estimation seems sufficiently precise for the large population analyzed and the duration and completeness of follow-up (1,126 patient-years, mean 101 months, 2 patients lost from follow-up), and it is in agreement with the estimations yielded by a literature review (1.8%). CONCLUSIONS: The risk of fulminant sepsis seems to be a real hazard in adults splenectomized for ITP, and a conservative approach in recommending splenectomy seems advisable. Antipneumococcal vaccination should also be recommended.

Adolescent↗

PubMedDate not supplied

Long-lasting remission after high-dose intravenous immunoglobulins in a case of relapsing thrombotic thrombocytopenic purpura.

Long-lasting remission after high-dose intravenous immunoglobulins in a case of relapsing thrombotic thrombocytopenic purpura (TTP) is reported. The patient had two early relapses after intensive plasma-exchange therapy. Serum platelet aggregating factor was absent. High-dose intravenous immunoglobulins (i.v. Ig) (0.4 g/Kg/day for 5 days) were infused. Platelet count promptly rose and 7 days after the completion of immunoglobulins complete response was obtained. The patient is still in complete remission, without further Ig infusion, 19 months later. This case adds to the anecdotal reports on the effectiveness of Ig, even when not associated with other treatments, in TTP. High-dose i.v. Ig could be successfully used in relapsing or unresponsive patients with TTP.

Blood Coagulation Factors↗

PubMedDate not supplied

Fibrinolytic studies in 13 unrelated families with factor XII deficiency.

BACKGROUND AND METHODS: We report the results of extensive "in vitro" fibrinolytic studies in 18 homozygous and 14 obligatory heterozygous subjects belonging to 13 unrelated families with factor XII deficiency. All homozygotes had unmeasurable factor XII activity (XII:C) and antigen (XII:Ag). None had bleeding symptoms, whereas a myocardial infarction occurred in one of them at age 51. In heterozygotes XII:C and XII:Ag were 55.9 +/- 14.1% and 52.1 +/- 16.4% (corresponding figures in 40 normals 100.6 +/- 18.3% and 101.5 +/- 29.7%). Total intrinsic fibrinolytic activity was assayed on fibrin plates in the dextran sulfate euglobulin fraction of plasma from resting subjects, to which flufenamate was added to inhibit blood plasminogen activator inhibitors. RESULTS: Fibrinolytic activity was reduced in all homozygotes (40 +/- 12 BAU/ml) in comparison to heterozygotes (103 +/- 12 BAU/ml) and normals (98 +/- 20 BAU/ml). The addition of purified activated beta-XII led to a complete restoration of fibrinolysis in homozygotes. The addition of anti-urokinase antibodies completely suppressed the reduced intrinsic fibrinolytic activity in homozygotes (4 +/- 7 BAU/ml), whereas a reduction to about 50% was evident in heterozygotes and normals. CONCLUSIONS: Our data confirm that reduced "in vitro" intrinsic fibrinolytic activity is a common finding in homozygous factor XII deficiency and that two independent mechanisms, one factor XII-dependent and urokinase-independent and the other factor XII-independent and urokinase-dependent, are responsible for the generation of intrinsic fibrinolysis in human plasma.

Adolescent↗

PubMedDate not supplied

Thrombotic complications during L-asparaginase treatment for acute lymphocytic leukemia.

We report 2 new cases of thrombosis occurring in a cohort of 21 consecutive patients with acute lymphocytic leukemia treated with L-asparaginase (L-ase), 6,000 U/die s.c. or i.m. days 15-21 from start of chemotherapy, according to the GIMEMA LAL 0288 protocol. The first patient died of massive diffuse thromboembolism (thrombosis of sagittal sinus and of suprahepatic veins and pulmonary arteries; multiple hepatic and splenic infarctions) associated with markedly reduced levels of protein C, antithrombin III and plasminogen. In the second patient, portal vein thrombosis developed soon after the completion of L-ase. Antithrombin III was reduced, whereas protein C level was normal. Therapy with fresh frozen plasma and subcutaneous calcium heparin (12,500 U twice daily) proved successful, and 8 days later abdominal echotomography revealed the complete disappearance of the thrombus. The incidence of thrombosis is similar to that previously found in a cohort of consecutive patients treated at our Department with a different schedule and dosage of L-ase administration, and similar to that reported in previous series.

Adolescent↗