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1.
J Endocrinol Invest ; 40(11): 1235-1241, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28528434

ABSTRACT

PURPOSE: Tall cell (TCV) and diffuse sclerosing (DSV) variants are aggressive variants of papillary thyroid cancer (PTC). We compared the risk of recurrent/persistent disease in patients with TCV, DSV and classical PTC (cPTC) and evaluated the prognostic accuracy of initial vs. ongoing risk stratification. METHODS: A consecutive series of DSV (n = 54), TCV (n = 72) and cPTC (n = 184) patients was retrospectively analyzed. TCV and DSV patients were first risk stratified for recurrent/persistent disease without considering the histotype as a risk factor and subsequently, 6-24 months after initial treatment, re-classified on the basis of the response to therapy (ongoing risk stratification). RESULTS: Extrathyroidal extension was more frequent in DSV than in TCV and cPTC patients (p < 0.05); moreover, only DSV tumors had a higher rate of recurrent/persistent disease when compared to cPTC treated with the same protocol (total thyroidectomy followed by 131I treatment) (p < 0.01). After initial treatment, 54.2% of TCV and 20.4% of DSV patients were classified at low risk, while at ongoing risk stratification, the excellent response (low risk) was higher for both TCV (77.8%) and DSV (50.0%) patients relative to initial stratification (both p < 0.01). Using ongoing risk classification, positive predictive value (PPV) for persistent/recurrent disease was higher relative to initial risk stratification for both TCV (PPV = 93.8 vs. 39.4%) and DSV (PPV = 63.0 vs. 34.9%), p < 0.05 for both. CONCLUSIONS: In our series DSV, but not TCV patients, had poorer outcome than cPTC treated with the same protocol. Moreover, the ongoing risk stratification predicted outcome better than the initial classification in both TCV and DSV patients.


Subject(s)
Carcinoma, Papillary/pathology , Neoplasm Recurrence, Local/pathology , Thyroid Neoplasms/pathology , Adult , Carcinoma, Papillary/classification , Carcinoma, Papillary/surgery , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/surgery , Prognosis , Retrospective Studies , Risk Factors , Thyroid Neoplasms/classification , Thyroid Neoplasms/surgery
3.
J Endocrinol Invest ; 38(9): 977-85, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25840794

ABSTRACT

PURPOSE: Control of thyroid function in hyperthyroid women during pregnancy is based on antithyroid drugs (ATD) [propylthiouracil (PTU) and methimazole (MMI)]. While a teratogenic effect has been suggested for MMI and, more recently, for PTU, a clear demonstration is still lacking. Aim of this study was to assess the safety of ATD during pregnancy. METHODS: A total of 379 pregnancies were retrospectively recruited in eight Italian Departments of Endocrinology and divided in five groups: (1) MMI-treated and euthyroid throughout pregnancy (n = 89); (2) MMI-treated and hyperthyroid on at least two occasions (n = 35); (3) PTU-treated women and euthyroid throughout pregnancy (n = 32); (4) PTU-treated women and hyperthyroid on at least two occasions (n = 20); and (5) non-ATD-treated (n = 203). Data on maternal thyroid function, miscarriages, type of delivery, neonatal weight, length and TSH, perinatal complications and congenital malformation were analyzed. RESULTS: The gestational age at delivery, the rate of vaginal delivery, neonatal weight, length and neonatal TSH did not significantly differ among groups. In all groups, the rates of spontaneous miscarriage and of major congenital malformations were not higher than in the general population. No newborns were born with a phenotype similar to those described in the "MMI embryopathy". CONCLUSIONS: While a clear demonstration of a teratogenic effect of MMI is currently lacking, it seems reasonable to follow the current guidelines and advice for PTU treatment in hyperthyroid women during the first trimester of pregnancy. Further, large and prospective worldwide studies will be needed to fully clarify the issue of ATD safety during pregnancy.


Subject(s)
Antithyroid Agents/therapeutic use , Hyperthyroidism/drug therapy , Methimazole/therapeutic use , Pregnancy Complications/drug therapy , Propylthiouracil/therapeutic use , Adult , Antithyroid Agents/adverse effects , Female , Graves Disease/drug therapy , Humans , Infant, Newborn , Methimazole/adverse effects , Pregnancy , Pregnancy Outcome , Propylthiouracil/adverse effects , Prospective Studies , Retrospective Studies
5.
J Endocrinol Invest ; 28(2): 106-12, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15887854

ABSTRACT

Human galectin-3 (hgal-3) is a beta-galactoside binding protein involved in a number of physiological and pathological processes. Increasing hgal-3 immunoexpression has been reported in several human tumors, including thyroid carcinomas, but not in benign thyroid lesions. We analyzed the immunolocalization of hgal-3 in cell compartments of benign and malignant thyroid lesions. Hgal-3 immunoperoxidase reaction was carried out on 133 thyroid tissue samples obtained from 113 patients; 20 of these were normal (NT), 85 were benign thyroid lesions [20 colloid nodules (CN), 21 nodular hyperplasias (NH), 7 focal lymphocytic thyroiditis (FLT), 15 Hashimoto's thyroiditis (HT), 22 follicular adenomas (FA)], 25 differentiated carcinomas [15 papillary carcinomas (PC), 6 follicular carcinomas (FC) and 4 Hürthle cell carcinomas (HC)] and 3 anaplastic carcinomas (AC). Among the malignant thyroid lesions, hgal-3 was detected in 12/15 (80%) PC, 3/4 (75%) HC and in 4/6 (66.6%) FC, but in none of the 3 AC. Conversely, hgal-3 immunoexpression was absent in NT and in all benign thyroid lesions, but 1/15 HT and 10/22 (45.4%) FA. In the latter, hgal-3 was mostly expressed in microfollicular areas and in five of the six atypical FA. Hgal-3 cytoplasmic-perinuclear immunolocalization was observed in the majority of thyroid carcinomas and in more than half of the FA, theoretically suggesting an involvement of this protein in thyroid tumorigenesis throughout an antiapoptotic activity. Moreover, hgal-3 expression in FA might anticipate the likelihood of evolution of these benign lesions towards malignancy.


Subject(s)
Adenoma/chemistry , Adenoma/pathology , Galectin 3/analysis , Thyroid Neoplasms/chemistry , Thyroid Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Humans , Immunohistochemistry/methods , Middle Aged , Staining and Labeling , Thyroid Diseases/metabolism , Thyroid Diseases/pathology , Thyroid Gland/chemistry , Tissue Distribution
6.
J Clin Endocrinol Metab ; 89(12): 6054-60, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15579758

ABSTRACT

Over a period of almost 10 yr, we carried out a prospective study of the neuropsychological development of the offspring of 16 women from a moderately iodine-deficient area (area A) and of 11 control women from a marginally iodine-sufficient area (area B) whose thyroid function had been monitored during early gestation. Attention deficit and hyperactivity disorder (ADHD) was diagnosed in 11 of 16 area A children (68.7%) but in none from area B. Total intelligence quotient score was lower in area A than in area B children (92.1 +/- 7.8 vs. 110 +/- 10) and in ADHD children when compared with both non-ADHD children from the same area and control children (88.0 +/- 6.9 vs. 99.0 +/- 2.0 and 110 +/- 10, respectively). Seven of 11 ADHD children (63.6%) were born to the seven of eight area A mothers who became hypothyroxinemic at early gestation, whereas only one of five non-ADHD children was born to a woman who was hypothyroxinemic at 20 wk of gestation. So far, a similar prevalence of ADHD has been reported only in children with generalized resistance to thyroid hormones. This might suggest a common ADHD pathogenetic mechanism consisting either of reduced sensitivity of the nuclear receptors to thyroid hormone (generalized resistance to thyroid hormones) or reduced availability of intracellular T3 for nuclear receptor binding. The latter would be the ultimate consequence of maternal hypothyroxinemia (due to iodine deficiency), resulting in a critical reduction of the source of the intracellular T3 available to the developing fetal brain.


Subject(s)
Attention Deficit Disorder with Hyperactivity/etiology , Developed Countries , Iodine/deficiency , Pregnancy Complications , Attention Deficit Disorder with Hyperactivity/psychology , Case-Control Studies , Child, Preschool , Deficiency Diseases/complications , Deficiency Diseases/physiopathology , Deficiency Diseases/psychology , Female , Humans , Infant , Intelligence , Italy , Mental Disorders/etiology , Nervous System Diseases/etiology , Pregnancy , Pregnancy Complications/physiopathology , Thyroid Gland/physiopathology
7.
Bone Marrow Transplant ; 33(11): 1097-105, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15094744

ABSTRACT

From July 1995 to December 2001, 42 patients with leukemia aged 1-42 years underwent cord blood transplant (CBT) from unrelated, < or = 2 antigen HLA mismatched donors. In all, 26 patients were in < or = 2nd complete remission and 16 in more advanced phase. Conditioning regimens, graft-versus-host disease (GVHD) prophylaxis and supportive policy were uniform for all patients. The cumulative incidence of engraftment was 90% (95% CI: 0.78-0.91). The cumulative incidence of III-IV grade acute- and chronic-GVHD was 9% (95% CI: 0.04-0.24) and 35% (95% CI: 0.21-0.60), respectively. The 4-year cumulative incidence of transplant-related mortality (TRM) and relapse was 28% (95% CI: 0.17-0.47) and 25% (95% CI: 0.14-0.45), respectively. The 4-year overall survival (OS), leukemia-free survival (LFS) and event-free survival (EFS) were 45% (95% CI: 0.27-0.63), 47% (95% CI: 0.30-0.64) and 46% (95% CI: 0.30-0.62), respectively. In multivariate analysis, the most important factor affecting outcomes was the CFU-GM dose, associated with CMV serology (P=0.003 and 0.04, respectively) in influencing OS and with patient sex (P=0.008 and 0.03, respectively) in influencing LFS. Finally, CFU-GM dose was the only factor that affected EFS significantly (P=0.02). In conclusion, the infused cell dose expressed as in vitro progenitor cell growth is highly predictive of outcomes after an unrelated CBT and should be considered the main parameter in selecting cord blood units for transplant.


Subject(s)
Cord Blood Stem Cell Transplantation/statistics & numerical data , Leukemia/therapy , Adolescent , Adult , Cell Count , Child , Child, Preschool , Cord Blood Stem Cell Transplantation/adverse effects , Cord Blood Stem Cell Transplantation/mortality , Female , Graft Survival , Graft vs Host Disease , Hematopoietic Stem Cells/cytology , Humans , Infant , Leukemia/diagnosis , Leukemia/mortality , Longitudinal Studies , Male , Prognosis , Risk Factors , Survival Analysis , Tissue Donors , Treatment Outcome
8.
Leukemia ; 17(10): 1930-3, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14513040

ABSTRACT

In all, 17 consecutive patients in hematological complete remission (HCR) of acute promyelocytic leukemia (APL) received allogeneic stem cell transplantation (SCT) from an HLA-identical sibling and were monitored by reverse transcriptase polymerase chain reaction of PML/RARalpha prior and after transplant. Median age was 31 years (range 3-50 years). At 10 years, the actuarial probabilities of nonrelapse mortality, relapse and disease-free survival were 32% (95% CI: 8-56%), 33% (95% CI: 6-60%) and 46% (95% CI: 22-70%). Six patients tested PCR +ve (1st HCR n=2; 2nd HCR n=3; 3rd HCR n=1) and 11 PCR -ve (2nd HCR n=11) pre-SCT. Of the six patients PCR +ve, two showed early persistence of PCR positivity and converted to sustained PCR negativity after CSA withdrawal (one died of secondary tumor in molecular remission and one is alive in relapse), while four converted to PCR -ve rapidly (one died of the underlying disease and three are in molecular remission). Of the 11 patients PCR -ve pre-SCT, six died (four of transplant-related mortality, one of relapse and one after heart transplantation) and five are alive, four in molecular remission and one is in relapse. Allogeneic SCT seems a valid option for advanced APL, particularly for the poor prognostic group of patients with pre-SCT molecularly persistent disease.


Subject(s)
Leukemia, Promyelocytic, Acute/genetics , Leukemia, Promyelocytic, Acute/therapy , Neoplasm Proteins/genetics , Oncogene Proteins, Fusion/genetics , Stem Cell Transplantation , Adolescent , Adult , Child , Child, Preschool , Humans , Leukemia, Promyelocytic, Acute/mortality , Leukemia, Promyelocytic, Acute/pathology , Middle Aged , Neoplasm Staging , Prognosis , Reverse Transcriptase Polymerase Chain Reaction , Survival Analysis , Transplantation, Homologous , Treatment Outcome
9.
Eur J Clin Microbiol Infect Dis ; 19(9): 711-4, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11057507

ABSTRACT

Two cases of listeriosis in patients submitted to matched unrelated donor bone marrow transplantation are reported. The patients developed listerial septicemia and listerial septicemia with meningitis and encephalitis 39 and 29 days after transplantation, respectively. Including the present two cases, 19 Listeria monocytogenes infections in related and unrelated donor allogeneic bone marrow transplant recipients have been reported to date. Infection occurred earlier in unrelated donor transplant recipients. Listeriosis is a rare complication in allogeneic bone marrow transplant recipients; however, the widespread practice of performing transplants from a donor-alternative to a human leukocyte antigen-compatible sibling and, in this setting, the need for intensified immunosuppression may predict an increasing and earlier occurrence of listeriosis.


Subject(s)
Bone Marrow Transplantation/adverse effects , Listeria monocytogenes , Listeriosis/diagnosis , Adult , Bone Marrow Transplantation/methods , Child , Humans , Male , Transplantation, Homologous
10.
Thyroid ; 9(8): 781-6, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10482370

ABSTRACT

Circulating thyroglobulin antibodies (TgAb) and thyroperoxidase antibodies (TPOAb) were measured in 143 iodine-deficient children, 5 to 15 years of age, from the Region of Tula, Russia, who had been moderately contaminated after the Chernobyl disaster (37-185 GBq/km2 of caesium-137, [group A]) and in 40 sex- and age-matched subjects from an uncontaminated neighboring area (<3.7 GBq/km2 of caesium-137, [group B]). Increased thyroid size at sonography was found in 41% and in 45% subjects from group A and group B, respectively, associated with supranormal thyrotropin (TSH) values in 7.7% of group A and 7.5% of group B, without differences in average serum free thyroxine (FT4), free triiodothyronine (FT3) and TSH. Serum thyroperoxidase antibody (TPOAb)-associated or not with thyroglobulin-antibody (TgAb) as detected in 18.9% of children and adolescents from group A, about four-fold higher than in group B (5%, Fischer's exact test p<0.05). A 24% frequency was found in subjects whose age, at the moment of the disaster was 0-72 months or were in utero, but the frequency was about 7%, similar to that in group B, in those who had not yet been conceived at that time. Less than half of antibody-positive group A children were hyperthyrotropinemic, whereas no group B subclinical hypothyroid subject was antibody-positive, thus excluding the autoimmune etiology of the subclinical thyroid failure; more likely it is attributable to iodine malnutrition. The high prevalence of humoral thyroid autoimmunity phenomena in the investigated area suggests a combined role of iodine malnutrition in enhancing the effects of short lived iodine isotopes, particularly evident in pubertal individuals conceived or born immediately before the Chernobyl disaster.


Subject(s)
Iodine/deficiency , Radioactive Hazard Release , Thyroiditis, Autoimmune/epidemiology , Adolescent , Age Factors , Autoantibodies/immunology , Child , Child, Preschool , Female , Goiter/epidemiology , Goiter/immunology , Humans , Immunoglobulins, Thyroid-Stimulating , Iodide Peroxidase/immunology , Male , Russia/epidemiology , Thyroglobulin/immunology , Thyroid Function Tests , Ukraine
11.
Thyroid ; 9(4): 387-91, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10319946

ABSTRACT

Twenty-five patients from a marginally iodine-deficient area with differentiated thyroid cancer who were referred to our unit between 1991 and 1997 had a residual thyroid uptake (RTU) at 24 hours of 5% or more after surgery. None of them underwent reoperation: 8 of 25 had RTU between 5% and 10% and were considered at low risk for both local recurrences and/or distant metastases; 17 of 25 had RTU greater than 10% and up to 30% and refused re-intervention. After detection of their cervical uptake by using a 131I tracer dose of 3.7 MBq (100 microCi), all 25 were treated with 1110 MBq (30 mCi) of 131I. A whole-body scan (WBS) performed 5 days later revealed 131I uptake corresponding to metastatic lymph nodes in the anterior part of the neck in 1 patient and the persistence of only RTU in 24 of 25 patients. RTU and thyroglobulin (Tg) levels were reevaluated 6 months later in all patients and compared to preradioiodine treatment values. RTU, ranging at presentation between 5% and 30%, decreased to below 1% in all but one patient. Serum Tg values, ranging between 1.6 and 108 ng/mL before radioiodine treatment, decreased to below 1.6 ng/mL in all but 4 of them (whose serum Tg was between 2 and 3.4 ng/mL). Our data indicate that 1,110 MBq of 131I can permit complete ablation of 80% of thyroid remnants concentrating up to 30% of radioiodine activity. A relation between this high success rate and iodine deficiency can be hypothesized because an increasing uptake of radioiodine by thyroid remnants could result in overestimation of their size. Therefore, our observations suggest that in iodine deficient areas, a hasty decision to carry out complete thyroidectomy should be avoided, even in the case of thyroid remnants with RTU up to 30%.


Subject(s)
Carcinoma/radiotherapy , Carcinoma/surgery , Iodine Radioisotopes/administration & dosage , Neoplasm, Residual/radiotherapy , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery , Thyroidectomy , Adolescent , Adult , Aged , Carcinoma/blood , Female , Humans , Iodine Radioisotopes/therapeutic use , Male , Middle Aged , Neoplasm, Residual/diagnostic imaging , Neoplasm, Residual/metabolism , Retrospective Studies , Thyroglobulin/blood , Thyroid Gland/radiation effects , Thyroid Gland/surgery , Thyroid Neoplasms/blood , Treatment Outcome , Ultrasonography
12.
Bone Marrow Transplant ; 23(6): 549-54, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10217184

ABSTRACT

In the last 3 years, 14 children with high-risk leukemia (11 ALL, 2 AML and 1 CML) underwent cord blood transplantation from unrelated HLA-mismatched donors at a median of 99 days from the start of search. Eight patients were transplanted in second CR, one in accelerated phase, three at relapse and two patients in first CR. Conditioning regimen (fractionated TBI, etoposide, CY and anti-lymphocyte serum) and prophylaxis of GVHD (CsA and 6-methylprednisolone) were identical for all patients. Neutrophils >0.5x10(9)/l were reached at a median of 33 days from transplant, but in four cases we observed an autologous hematopoietic reconstitution (three spontaneous, one after autologous BM rescue). Acute and chronic GVHD were observed in 10/14 and 3/8 evaluable cases, respectively. Three patients died of transplant-related toxicity and three patients relapsed. The probabilities of event-free, disease-free and overall survival were 50, 53 and 64%, respectively. Cord blood transplant from HLA-mismatched unrelated donor is a valid option for the treatment of children with high-risk leukemia. With our eligibility criteria, conditioning regimen and prophylaxis of graft-versus-host disease, the main obstacles to successful transplant were represented by graft failure and fatal acute GVHD.


Subject(s)
Fetal Blood , Fetal Tissue Transplantation , HLA Antigens/blood , Leukemia/therapy , Adolescent , Child , Child, Preschool , Female , Fetal Tissue Transplantation/adverse effects , Fetal Tissue Transplantation/immunology , Graft vs Host Disease/etiology , Histocompatibility Testing , Humans , Leukemia/epidemiology , Male , Risk Factors , Tissue Banks , Tissue Donors , Transplantation Chimera , Treatment Outcome
13.
Br J Haematol ; 104(4): 770-7, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10192439

ABSTRACT

We prospectively studied the chimaerism status in the bone marrow (BM) and peripheral blood (PB) of 23 patients receiving umbilical cord (UCB, 14 cases) or BM (nine cases) transplants from unrelated donors by PCR amplification of four individual-specific VNTR genetic loci. Haematological engraftment, with persistent full donor pattern. was observed in 10/14 (72%) patients receiving UCB and in 9/9 (100%) patients transplanted with marrow from an unrelated donor (MUD). In contrast, the remaining four patients converted to an autologous pattern. Three out of these four patients had an early autologous haematological reconstitution reaching a neutrophil level >0.5 x 10(9)/l at days 27, 33 and 37 after transplant, respectively. In all three of these patients, chimaerism analysis demonstrated an early appearance of donor cells (i.e. within 35 d after UCB transplant) showing a transient full donor (one case) or mixed chimaerism condition (two cases). Despite the early autologous haemopoietic reconstitution, one of the three patients died of GVHD at day 60, which was explained by the demonstration of low levels of donor lymphoid cells. In the MUD group all nine patients converted to a persistent full donor pattern with haematological reconstitution, accompanied in two of them by transient mixed chimaerism lasting to days 60 and 270 after transplant. Our data show that monitoring of chimaerism may predict graft failure with or without early autologous haemopoietic reconstitution in patients receiving unrelated UCB transplants. Furthermore, chimaerism analysis may identify, in patients with autologous reconstitution, those at risk of severe GVHD in whom immunosuppressive therapy should not be discontinued.


Subject(s)
Bone Marrow Transplantation/methods , Fetal Blood , Hematologic Neoplasms/therapy , Adolescent , Child , Female , Graft Survival , Hematologic Neoplasms/genetics , Humans , Male , Prospective Studies , Transplantation Chimera , Transplantation, Autologous
14.
Thyroid ; 9(1): 19-24, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10037071

ABSTRACT

In an effort to assess the impact of moderate iodine deficiency on maternal thyroid function during pregnancy, we measured serum thyrotropin, total and free thyroid hormones, thyroid-binding globulin (TGB) at 8, 14, 20, 29, and 36 weeks of gestation, along with urinary iodide excretion, in 10 healthy women from a moderately iodine deficient region (group A), and compared them with 6 women from an iodine sufficient region (group B). Serum total thyroxine (T4) fell significantly in group A, and was significantly lower than in group B at 29 and 36 weeks (p<0.05). TBG saturation was significantly lower in group A throughout pregnancy, and declined in both groups as pregnancy progressed. Free thyroxine (T4) and triiodothyronine (T3) concentrations fell in both groups, and FT4 values were significantly lower in group A than group B in the third trimester (p<0.05). Urinary iodine excretion was lower in group A women with respect to group B and did not vary significantly in either group as gestation progressed. The serum T3/T4 molar ratio increased through pregnancy only in group B. Thyrotropin concentrations rose in both groups through pregnancy, and were higher in group A at term (p< 0.01). The incidence of isolated hypothyroxinemia or biochemical hypothyroidism doubled (30% to 70%) between midgestation and term in group A, suggesting that moderate iodine deficiency may result in maternal thyroid failure during the later stages of pregnancy.


Subject(s)
Hypothyroidism/epidemiology , Iodine/deficiency , Pregnancy Complications/epidemiology , Thyroid Gland/physiopathology , Adult , Female , Gestational Age , Humans , Hypothyroidism/blood , Hypothyroidism/physiopathology , Iodine/urine , Pregnancy , Pregnancy Complications/blood , Pregnancy Complications/physiopathology , Risk Factors , Thyroid Function Tests , Thyrotropin/blood , Thyrotropin/metabolism , Thyroxine/blood , Thyroxine-Binding Proteins/metabolism , Triiodothyronine/blood
15.
Bone Marrow Transplant ; 21 Suppl 3: S85-6, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9712504

ABSTRACT

Twelve consecutive children with high-risk leukemia have been submitted to UCB transplant from unrelated 1 or 2 loci HLA-mismatched donor. All patients received an identical regimen for conditioning and GVHD prophylaxis. The median dose of viable nucleated cells infused was 2.8 x 10(7)/kg bw (range 1.4-7.9). Of 11 patients evaluable for engraftment, the hematopoiesis was of full donor origin in seven patients and autologous in four. The probability of disease-free survival at 1 and 2 years from UCB transplant is 60 and 42%, respectively.


Subject(s)
Fetal Blood , Hematopoietic Stem Cell Transplantation , Leukemia/therapy , Adolescent , Child , Child, Preschool , Disease-Free Survival , Female , Fetal Tissue Transplantation , Histocompatibility Testing , Humans , Male , Transplantation, Homologous , Treatment Outcome
16.
Bone Marrow Transplant ; 22 Suppl 1: S75, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9715896

ABSTRACT

Ten consecutive children with high risk leukemia have been submitted to UCB transplant from unrelated HLA mismatched donors. All patients received an identical regimen for conditioning and GVHD prophylaxis. The median dose of viable nucleated cells infused was 2.6 x 10(6)/kg b.w. Among the nine patients evaluable for engraftment the hematopoiesis was of full donor origin in six patients and autologous in three. At a median follow-up of 9 months, six of nine (67%) patients are alive in CR.


Subject(s)
Fetal Blood , Hematopoietic Stem Cell Transplantation , Leukemia/therapy , Adolescent , Child , Child, Preschool , Female , Fetal Blood/immunology , Graft vs Host Disease/immunology , Graft vs Host Disease/prevention & control , Hematopoiesis/immunology , Hematopoietic Stem Cells/immunology , Histocompatibility Testing , Humans , Male , Risk Factors , Transplantation Conditioning , Treatment Outcome
17.
Leuk Lymphoma ; 32(1-2): 89-95, 1998 Dec.
Article in English | MEDLINE | ID: mdl-10037004

ABSTRACT

Fifty-seven patients aged < 55 years with acute lymphoblastic leukemia (ALL) in second or third bone marrow (BM) relapse or refractory to first-line therapy were enrolled in an Italian cooperative study. The ALL R-87 protocol included idarubicin (IDA) plus intermediate dose cytarabine (IDARA-C) and Prednisone (PDN) as induction, followed by a consolidation phase and BMT. Complete remission (CR) was achieved in 41/57 patients (72%). The CR rate was significantly higher in patients aged < 15 years at diagnosis and at time of treatment compared to those aged > or = 15 (84% vs 50%, p=0.01 and 85% vs 54%, p = 0.02, respectively). Nineteen of 41 responders (46.3%) underwent bone marrow transplant (BMT) (10 autologous and 9 allogeneic). The estimated probabilities of event free survival (EFS +/- SE) and survival +/- SE at 6 years were 0.13 +/- 0.05 and 0.20 +/- 0.06, respectively, for all enrolled patients. Univariate analysis showed that children had a better EFS rate compared to adults (0.16 +/- 0.07 vs 0.08 +/- 0.07, p = 0.014). The estimated probability of disease free survival (DFS +/- SE) at 6 years was 0.18 +/- 0.07 for all responders. No differences in DFS were observed between patients submitted to allogeneic or autologous BMT (0.33 +/- 0.16 vs 0.25 +/- 0.15). Among patients treated in second or third relapse, a first CR length > or = 48 months favorably influenced both DFS (p = 0.014) and EFS (p = 0.018). Our results show the efficacy of the intermediate dose ARA-C plus IDA schedule for high risk adult and childhood ALL patients. No differences in disease outcome were observed between allogeneic and autologous BMT.


Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Age Factors , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Transplantation , Child , Child, Preschool , Cytarabine/administration & dosage , Disease-Free Survival , Female , Humans , Idarubicin/administration & dosage , Infant , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prednisone/administration & dosage , Recurrence , Remission Induction , Survival Rate , Treatment Outcome
18.
Br J Haematol ; 99(3): 671-7, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9401083

ABSTRACT

Seventy-three children with acute lymphoblastic leukaemia (ALL) in first bone marrow (BM) relapse, occurring within 30 months from complete remission (CR), were enrolled in an Italian cooperative study (ALL R-87 protocol). This treatment programme consisted of an induction phase with intermediate-dose cytarabine (IDARA-C) plus idarubicin (IDA) and prednisone (PDN), followed by a multidrug consolidation therapy and bone marrow transplant (BMT). 55/73 children achieved CR (75.3%); 15 (20.5%) failed to respond and three (4.2%) died during induction. The response rate was significantly higher for children with a first CR duration > or = 12 months (P=0.0005) and for those with a white blood cell (WBC) count at relapse < 20 x 10(9)/l (P=0.004). The estimated disease-free survival (DFS +/- SE) at 82 months was 0.18 +/- 0.05 for all responders, and 0.70 +/- 0.14 for allotransplanted patients versus 0.05 +/- 0.05 for those autografted (P=0.001). The estimated probabilities of survival +/- SE and event-free survival (EFS +/- SE) at 83 months were 0.16 +/- 0.07 and 0.13 +/- 0.04, respectively. for all enrolled children. Univariate analysis showed that age < 10 years at initial diagnosis and B-lineage immunophenotype favourably influenced both DFS (P=0.001) and EFS probabilities (P=0.0014 and P=0.012, respectively), whereas a first CR duration > or = 12 months and a WBC count at relapse < 20 x 10(9)/l were associated only with a better EFS rate (P=0.026 and P=0.004, respectively). Our results show the efficacy of the IDA plus IDARA-C schedule used in the ALL R-87 protocol in high-risk relapsed ALL children. Allogeneic BMT proved effective for patients with an HLA sibling donor. In a multivariate analysis, age > or = 10 years at initial diagnosis (P=0.016) and WBC count at relapse > or = 20 x 10(9)/l (P=0.048) were independently associated with a worse disease outcome.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Age Factors , Child , Child, Preschool , Cytarabine/administration & dosage , Disease-Free Survival , Female , Humans , Idarubicin/administration & dosage , Infant , Leukocyte Count , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Prednisone/administration & dosage , Prospective Studies , Recurrence , Risk Factors , Survival Analysis , Survival Rate , Treatment Outcome
19.
Haematologica ; 82(5 Suppl): 19-22, 1997.
Article in English | MEDLINE | ID: mdl-9402749

ABSTRACT

BACKGROUND AND OBJECTIVE: The anthracycline analogue idarubicin, either alone or in combination with other antineoplastic drugs, has shown antileukemic activity in relapsed and refractory acute lymphoblastic leukemia (ALL). In an attempt to minimize the non-hematologic toxicity and obtain a potent antileukemic effect, MSKCC activated a pilot study in previously treated adult ALL, using HD-ARA-C combined with idarubicin administered as a single high-dose infusion. We herein report our experience with a series of pediatric and adult high risk ALL and NHL patients treated with the protocol above, which confirms its feasibility, response rate and individual compliance. METHODS: In a clinical phase II study the combination of a single high dose (HD) idarubicin and HD cytosine-arabinoside (ARA-C), as designed at the Memorial Sloan Kettering Cancer Center, was applied to 70 adults and children with refractory or early relapse acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic non-Hodgkin's lymphoma (NHL). Therapy consisted of HD-ARA-C 3 g/m2/d on days 1-5, idarubicin 40 mg/m2 on day 3, prophylactic intrathecal methotrexate on days 1 and 4, and G-CSF 5 mg/kg/d s.c. from day 7 to hematopoietic reconstitution (PMN > 0.5 x 10(9)/L). RESULTS: Fifty-five of the 70 patients (78%) achieved complete remission (CR), four died in aplasia due to infection and 11 were non-responders. Recovery of blood counts occurred at a median of 21 days from the start of treatment. Non-hematologic side effects were extremely limited and consisted predominantly of infections. INTERPRETATION AND CONCLUSIONS: In view of the highly unfavorable series of patients selected, this study confirms the feasibility and antileukemic activity of the HD-idarubicin + HD- ARA-C combination in patients with refractory and early relapse ALL and NHL. The excellent tolerance to this regimen does not preclude bone marrow transplantation as post-remission treatment.


Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Cytarabine/therapeutic use , Idarubicin/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Humans , Infant , Male , Rome , Universities
20.
Cancer ; 80(9): 1786-91, 1997 Nov 01.
Article in English | MEDLINE | ID: mdl-9351548

ABSTRACT

BACKGROUND: Langerhans' cell histiocytosis (LCH) is a rare disorder of uncertain etiology, characterized by a wide clinical spectrum and varied behavior. METHODS: This retrospective study analyzed 11 adult patients with a diagnosis of LCH observed at the study institution between April 1988 and March 1993. RESULTS: Based on the sites and extent of disease at diagnosis, patients were divided into four categories. Group A was comprised of four patients with unifocal bone disease who had surgical curettage. At last follow-up only 1 patient was in continuous complete response (CCR) at 29+ months. The other 3 patients recurred at 3, 12, and 30 months, respectively, after surgery and at last follow-up were found to be in CR at 16+, 48+, and 124+ months, respectively, after therapy with vinblastine (VBL) and high dose methylprednisolone (HDMP). Group B was comprised of three patients with multifocal bone disease. Two of these patients received VBL + HDMP; at last follow-up, 1 patient was in CCR 8 months after completion of therapy, and the other developed progressive disease 11 months later. The third patient was treated with interferon (IFN) and at last follow-up was in CCR at 35+ months. Group C was comprised of 2 patients with bone and visceral disease who were treated with etoposide (VP-16) + HDMP; at last follow-up, 1 patient was in CCR at 42+ months and the other patient, who had isolated vulvar recurrence 16 months later, was in CR with treatment with local IFN. Group D was comprised of two patients with lung and lymph node involvement, one of whom was treated with VP-16 + HDMP and the other with cyclophosphamide, doxorubicin, vincristine, and prednisone; at last follow-up, both were in CCR at 30+ and 71+ months, respectively. CONCLUSIONS: VBL + HDMP showed efficacy in patients with bone disease, in particular those treated for recurrent LCH after surgery. Therapy with VP-16 and HDMP was successfully employed in patients with visceral disease. IFN was effective both for localized disease and in patients with multiple bone lesions.


Subject(s)
Histiocytosis, Langerhans-Cell/therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Diseases/therapy , Gastrointestinal Diseases/therapy , Histiocytosis, Langerhans-Cell/drug therapy , Histiocytosis, Langerhans-Cell/surgery , Humans , Interferons/therapeutic use , Lung Diseases/therapy , Lymphatic Diseases/therapy , Male , Methylprednisolone/therapeutic use , Retrospective Studies , Salvage Therapy , Treatment Outcome , Vinblastine/therapeutic use
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