Biomedical subjects

M Zecca

Publications and source records attributed to M Zecca.

At least 19 recordsLinked to original sources

PubMed1995

Alloantigen-induced human lymphocytes rendered nonresponsive by a combination of anti-CD80 monoclonal antibodies and cyclosporin-A suppress mixed lymphocyte reaction in vitro.

Induction of a state of long-term, alloantigen-specific T cell nonresponsiveness has significant implications for human transplantation. It has been previously described that alloantigen-specific anergy may be induced by addition of cyclosporin-A together with anti-CD80(B7-1) mAb to a MLR. In this study we endeavored to verify whether alloantigen-induced PBL rendered anergic by the addition of a combination of anti-B7 mAb and cyclosporin-A during a MLR had a suppressive effect when added to autologous lymphocytes activated in MLR. We found that: 1) the addition of cells rendered anergic by this procedure to a MLR suppress both proliferative and cytotoxic response of autologous responsive PBL to either the same or third-party stimulator cells; 2) the suppressive effect is limited to alloantigen-induced T cell activation, as addition of anergic cells does not influence mitogen- or antigen-induced proliferation of autologous responsive T cells; 3) nonresponsiveness of suppressed cells cannot be reversed by either subsequent restimulation with allogeneic cells or addition of exogenous IL-2 to the cultures; 4) the suppressive effect is apparently not due to secretion of anergic cell-derived soluble factors, but it seems to be dependent on cell-cell contact between anergic, responsive, and stimulator cells. These data suggest that: 1) the delivery of a direct signal mediated by anergic lymphocytes through a cell-cell contact is likely to be the mechanism responsible for the suppressive effect here described; 2) anergic cells may propagate alloantigen-specific tolerance to potentially responsive autologous lymphocytes. Preliminary experiments indicate that anti-CD86(B7-2) mAb may play a similar role in the generation of alloantigen-induced nonresponsiveness.

Antibodies, Monoclonal↗

PubMed1995

Role of busulfan and total body irradiation on growth of prepubertal children receiving bone marrow transplantation and results of treatment with recombinant human growth hormone.

Seventy-six prepubertal children receiving autologous or allogeneic bone marrow transplantation (BMT) were enrolled in a prospective study on the impact of different pretransplant preparative regimens on growth. Patients were divided into three groups: group I, consisting of 37 children who had received total body irradiation (TBI) and cytotoxic drugs as preparative regimen; group II, including 17 children receiving prophylactic cranial irradiation before being conditioned with TBI and cytotoxic drugs; and group III, composed of 22 patients transplanted after a busulfan (BU)-containing myeloablative therapy. All patients have a minimum follow-up of 2 years, whereas 48 and 34 patients have been studied until 3 and 4 years after transplant, respectively. Height and growth rate were expressed as standard deviation score (SDS). Growth hormone (GH) secretion in response to pharmacologic stimuli was evaluated after documented growth failure. Patients with GH deficiency were treated with recombinant human GH, and response to therapy was evaluated. The main impairment of growth rate in patients belonging to group II was observed in the first year after TBI (growth rate SDS changing from -0.12 +/- 0.23 to -1.23 +/- 0.25, P < .005), with only a slight loss in the following years, whereas in group I children growth failure occurred in the third year after TBI (-1.36 +/- 0.28 SDS in comparison to a pre-BMT SDS of 0.10 +/- 0.15, P < .005). Therefore, growth velocity between these two groups differed significantly in the first 2 years (P < .01) but subsequently equalized. On the contrary, all BU-treated children but 2 grew normally. GH deficiency was shown in the vast majority of children with growth impairment. Twenty-three children treated with recombinant human GH are evaluable; a successful response was observed in all but 1, with the mean growth rate increasing from -2.29 +/- 0.27 before treatment to 0.86 +/- 0.38 and to 1.66 +/- 0.56 SDS at 1 and 2 years after treatment, respectively (P < .001). In conclusion, growth rate impairment was common in patients receiving TBI, with the speed of onset of both decreased growth velocity and GH deficiency depending mainly on the total dose of radiation. On the contrary, patients receiving BU did not experience significant problems in terms of growth velocity. The timely start of appropriate hormonal replacement therapy may ameliorate the final growth of children undergoing BMT.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Juvenile chronic myelogenous leukemia: in vitro characterization before and after allogeneic bone marrow transplantation.

In previously published studies on patients with juvenile chronic myelogenous leukemia (JCML), excessive proliferation of malignant monocyte-macrophage elements and impaired growth of normal hematopoietic progenitors were demonstrated. A selective hypersentivity of granulocyte-macrophage progenitors (CFU-GM) to granulocyte-macrophage colony stimulating factor (GM-CSF) seems to represent the main pathogenetic mechanism. Allogeneic bone marrow transplantation (BMT) has been demonstrated to be the only curative strategy for patients with JCML. In this study, we evaluated the growth of peripheral blood hematopoietic progenitors in semisolid cultures in two children with JCML before and after allogeneic BMT. Serum levels of GM-CSF, interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) were also assessed. IL-1-beta, GM-CSF and TNF-alpha serum levels of the patients before and after BMT did not differ significantly from those obtained in 45 healthy controls. After marrow transplant, the engraftment of donor hematopoietic stem cell was associated with the disappearance of both pretransplant GM-CSF hypersensitivity and CFU-GM spontaneous growth. The inhibitory effect on the growth of normal hematopoietic progenitors also resolved. This confirms that the substitution of the pathological hematopoietic progenitors represents the basis for the curvative effect of allogeneic BMT in the treatment of JCML, abolishing both the excessive responsiveness of JCML progenitor cells even to very low concentrations of GM-CSF and the growth-inhibitory effect on normal hematopoiesis.

Bone Marrow Transplantation↗

PubMed1995

Antibody response to pneumococcal vaccine in children receiving bone marrow transplantation.

Fifty-three pediatric patients given an allogeneic or an autologous bone marrow transplantation (BMT) were immunized with a polyvalent pneumococcal capsular polysaccharide vaccine (Pneumovax II). Vaccine was administered six months or more after BMT and the pneumococcal IgM, total IgG, and IgG subclasses levels were evaluated before and three weeks after immunization. Immunization promoted a significant rise in antibody serum levels (P < 0.000001), and all children vaccinated more than two years after transplantation responded to pneumococcal polysaccharides, whereas only 20-30% and 50% of patients given BMT between six months and one year and one and two years, respectively, mounted an effective antibody production (P < 0.0001). In univariate analysis, lapse of time from BMT to vaccination, chronic graft-versus-host disease occurrence, and female sex influenced the response rate. However, in multivariate analysis, only time between marrow transplant and immunization was a powerful predictor of response. Interestingly, four of 11 patients with IgG2 deficiency before immunization normalized serum levels of this IgG subclass after the pneumococcal antigenic challenge. Our study suggests that time after transplant is the major factor influencing the recovery of immune reactivity to polysaccharide antigens. This seems to confirm the hypothesis that ontogeny of the B-cell repertoire follows a predetermined sequential program in which polysaccharide antigens are some of the last to evoke an antibody response.

Adolescent↗

PubMed1995

Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing.

The Drosophila wing is formed by two cell populations, the anterior and posterior compartments, which are distinguished by the activity of the selector gene engrailed (en) in posterior cells. Here, we show that en governs growth and patterning in both compartments by controlling the expression of the secreted proteins hedgehog (hh) and decapentaplegic (dpp) as well as the response of cells to these signaling molecules. First, we demonstrate that en activity programs wing cells to express hh whereas the absence of en activity programs them to respond to hh by expressing dpp. As a consequence, posterior cells secrete hh and induce a stripe of neighboring anterior cells across the compartment boundary to secrete dpp. Second, we demonstrate that dpp can exert a long-range organizing influence on surrounding wing tissue, specifying anterior or posterior pattern depending on the compartmental provenance, and hence the state of en activity, of the responding cells. Thus, dpp secreted by anterior cells along the compartment boundary has the capacity to organize the development of both compartments. Finally, we report evidence suggesting that dpp may exert its organizing influence by acting as a gradient morphogen in contrast to hh which appears to act principally as a short range inducer of dpp.

Animals↗

PubMed1995

Autologous bone marrow transplantation for acute myeloid leukaemia in children using total body irradiation and melphalan as conditioning regimen.

We conducted a phase II study on 19 children with AML in first (10 patients) or second (nine patients) complete remission (CR) treated with ABMT, evaluating the combination of total body irradiation (TBI, 12 Gy in six divided fractions) and high-dose melphalan (140 mg/m2 in single dose) in an attempt to improve antitumour efficacy of conditioning regimen. All patients received cryopreserved and in vitro purged (mafosfamide at a dose of 100 micrograms/ml) bone marrow. The median time from first CR to ABMT was 5 months compared with a median time of 3 months for patients in second remission. One of the 19 patients, transplanted in second CR, died of transplant-related complication 10 days after transplant and another second CR patient relapsed on day +28, before engraftment. Three further patients in second CR relapsed at 6, 6 and 18 months after marrow transplant, respectively, and this determined a relapse rate of 43% in children given ABMT in second CR and 0% for patients transplanted in first remission (P < 0.05). Seventy-two per cent of all patients are projected to be alive and disease-free at 6 years, whereas the event-free survival of patients in first and in second CR is 100 and 44%, respectively (P < 0.05). Although the number of patients does not allow us to draw any firm conclusion, our results are encouraging and suggest that the association of TBI and high-dose melphalan appears to be safe and valuable.

Adolescent↗

PubMed1994

Sustained remission of immune-mediated red cell aplasia in a child after intravenous administration of gamma globulin.

A 4-year-old white boy with immune-mediated red cell aplasia and severe anemia was given high intravenous doses of gamma-globulin. The therapy was well tolerated and followed by complete resolution of the inhibition of erythropoiesis with no recurrence of disease. Eight months after discontinuation of treatment, the patient has a normal complete blood cell count.

Bone Marrow↗

PubMed1994

Human cytomegalovirus (HCMV) infection in paediatric patients given allogeneic bone marrow transplantation: role of early antiviral treatment for HCMV antigenaemia on patients' outcome.

In a prospective study, we evaluated the role of early treatment with ganciclovir of human cytomegalovirus (HCMV) pp65-antigenaemia, as well as the risk factors related to the infection in 48 paediatric patients given an allogeneic bone marrow transplantation (BMT). HCMV infection occurred in 24 children, the overall actuarial risk of infection at 120 d being 51%. Development of acute graft-versus-host disease (GVHD), steroid therapy and serological status of both recipient and donor were the most powerful predictors of HCMV infection, none of the six seronegative patient/donor pairs developing HCMV infection. Considering only the seropositive recipients and patients given a seropositive marrow (42 cases), the actuarial risk of developing HCMV antigenaemia in patients with acute GVHD was 76% v 27% in those with or without GVHD (P < 0.005) and 79% v 15% respectively in patients who did or did not receive steroid therapy (P < 0.001). HCMV disease developed in 5/24 children with pp65-antigenaemia, which was detected before diagnosis in all cases but one. All patients with pp65-positive cells were treated with ganciclovir at a dose of 5 mg/kg twice daily for 14 d. In patients without acute GVHD no maintenance therapy was administered, whereas children with active acute GVHD were given additional therapy with ganciclovir at a dose of 5 mg/kg/d for 14 d. Ganciclovir produced complete clearing of viraemia and antigenaemia, with some patients presenting recurrences of antigenaemia, which were treated according to the above-mentioned schedule. Likewise, HCMV disease completely resolved after treatment with ganciclovir and no patients died from HCMV-related interstitial pneumonia. Our results suggest that an early short-term therapy with ganciclovir after demonstration of antigenaemia can be effective in reducing or abolishing HCMV-related mortality. This approach eliminates the use of ganciclovir in patients not presenting HCMV reactivation and therefore not benefiting from therapy. The administration of ganciclovir limited to the period needed to obtain antigenaemia clearance could also have the advantage of reducing myelotoxicity.

Adolescent↗

PubMed1994

Treatment of chronic childhood immune thrombocytopenic purpura with intramuscular anti-D immunoglobulins.

Seven patients with chronic immune thrombocytopenic purpura (ITP) were treated with intramuscular anti-D (anti-D IgG) five times, on an alternate-day basis, or until a platelet count of 100 x 10(9)/l was achieved, and, subsequently, when necessary to maintain platelet counts above 50 x 10(9)/l. Five patients responded to therapy, two of whom entered long-term remission. Although signs of haemolysis were present in all patients, anaemia was never a problem. No patient developed haematomas at the site of injection. We suggest that intramuscular anti-D represents a safe and relatively inexpensive alternative to intravenous gamma globulins (IVGG) for children with severe chronic ITP.

Adolescent↗

PubMed1994

Recombinant human erythropoietin may correct erythropoietin-deficient hyporegenerative anaemia in children given cardiac transplantation.

Cyclosporin-A reduces erythropoietin production and, together with the inhibitory effect of cytokines on erythropoiesis, may be potentially responsible for the anaemia observed in some patients after heart transplantation. Two children given cardiac transplantation and receiving cyclosporin-A developed transfusion-dependent hyporegenerative anaemia. Erythropoietin production was inappropriately low for the degree of anaemia, with an observed/predicted log(serum EPO) ratio of 0.54 and 0.49, respectively. The children were treated with rHuEPO at a dose of 75 U/kg three times weekly for 1 month and then twice weekly via subcutaneous injection. No further transfusion was necessary and restoration of normal erythroid activity was obtained, with normal haemoglobin values. No adverse effects were observed. Our experience suggests that recombinant human erythropoietin may be useful in treating the anaemia associated with cardiac transplantation.

Anemia↗

PubMed1994

Expression of p75 chain of IL-2 receptor in the early immunological reconstitution after allogeneic bone marrow transplantation.

Expression of p55 and p75 chains of IL-2 receptor (IL-2R) on the surface of both T and natural killer (NK) circulating lymphocytes was investigated in 14 paediatric patients given allogeneic bone marrow transplantation (BMT) from HLA-identical sibling or partially matched family donors. IL-2-induced proliferative and cytotoxic responses were also studied and all analysis was performed within 45 days from transplant. We found that, early after transplant, the percentage of p55+ and of p75+ peripheral blood lymphocytes (PBL) was not significantly different in patients who had received HLA-identical BMT (p55+ 8.04 +/- 4.87%; p75+ 28.27 +/- 18.85%) compared with healthy controls (p55+ 7.26 +/- 6.17%; p75+ 19.42 +/- 10.49%), while recipients of T cell-depleted marrow included a remarkably high percentage (76-90%) of p75+ PBL, which were mostly CD3- and co-expressed CD56 molecule. Comparable values of p55+ lymphocytes were observed in all patients and controls. However, in contrast to the other two groups, in recipients of T cell-depleted BMT the majority of these cells co-expressed p75 chain and CD56 antigen. IL-2-induced proliferation and lymphokine-activated killer (LAK) activity were detectable in all patients, and their values did not correlate with expression of p55 or p75 chains. Our data suggest that expansion of NK subsets expressing IL-2R chains after T cell-depleted BMT may be related to early reconstitution of natural immunity in the presence of allogeneic stimuli.

Adolescent↗

PubMed1994

Busulfan.

OBJECTIVE: To review the current published studies evaluating the pharmacokinetics, clinical efficacy, safety, and toxicity of busulfan in pediatric and adult patients. DATA SOURCES: English-language literature published between 1953 and 1993 was analyzed; pertinent literature was reviewed. STUDY SELECTION: Emphasis was placed on pharmacologic studies and clinical trials involving busulfan therapy both in myeloproliferative disorders and in conditioning regimens for autologous or allogeneic bone marrow transplantation. DATA EXTRACTION: Data from both pediatric and adult studies were evaluated; emphasis was placed on the relationship between plasma concentrations of busulfan and its efficacy and toxicity. DATA SYNTHESIS: Busulfan has been used widely at conventional dosages (1-12 mg/d) for the treatment of patients with chronic myelogenous leukemia (CML). Busulfan at high doses (usually 16 mg/kg) given with other cytotoxic drugs (especially cyclophosphamide) is a common preparative regimen in patients undergoing allogeneic or autologous bone marrow transplantation (BMT) for acute or chronic leukemia and other nonmalignant disorders (e.g., hemoglobinopathies, inborn error of immune system, congenital metabolic disorders). Pharmacokinetics of high-dose busulfan are age-dependent. Busulfan systemic exposure and, thus, tissue and tumor exposure are lower in children than with adults. Relationships between toxicity (principally neutropenia, hepatic veno-occlusive disease, incidence of seizures) and drug exposure were found for busulfan. CONCLUSIONS: Busulfan is a useful, sufficiently safe drug in the treatment of patients with CML. At higher dosages, busulfan is a fundamental part of myeloablative therapies for patients undergoing BMT. As the pharmacokinetics and metabolism of busulfan is further understood, there is great potential for improving treatment outcome. An assessment of maximal tolerated exposure determined by therapeutic drug monitoring may decrease the incidence and lethality of regimen-related toxicities.

Age Factors↗

PubMed1994

Pilot trial of combined administration of erythropoietin and granulocyte colony-stimulating factor to children undergoing allogeneic bone marrow transplantation.

We carried out a pilot study to evaluate the combined use of recombinant human erythropoietin (rhEpo) and granulocyte colony-stimulating factor (G-CSF) for accelerating marrow engraftment in children given allogeneic bone marrow transplantation (BMT). Fifteen consecutive children were enrolled in this study; 13 completed it and were evaluable. Using analysis of variance, laboratory and clinical data referring to these children were compared with those of 15 patients previously treated with rhEpo alone and with those of 16 historical controls. Erythroid repopulation, evaluated sequentially through serum transferrin receptor and reticulocyte count, was similarly accelerated in children receiving rhEpo alone and in those receiving combined treatment. These latter, however, showed a further reduction in the total number of red blood cell units required to reach transfusion independence (1.1 +/- 0.7 in the study population vs 2.7 +/- 1.2 in rhEpo group vs 4.2 +/- 2.3 in historical controls; values are mean +/- 1 SD; p < 0.001). Neutrophil engraftment, i.e. time for neutrophils to reach 0.5 x 10(9)/l, was 11 +/- 3 days in children receiving combined treatment, significantly shorter than that of the control groups (16 +/- 3 and 18 +/- 5, respectively; p < 0.001). Acceleration of neutrophil recovery translated into fewer infections: days of fever were significantly reduced in the study population (4 +/- 2 vs 11 +/- 8 vs 15 +/- 6, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Use of recombinant human erythropoietin after bone marrow transplantation in pediatric patients with acute leukemia: effect on erythroid repopulation in autologous versus allogeneic transplants.

We carried out a pilot study on the use of recombinant human erythropoietin (rHuEPO) in children undergoing allogeneic or mafosfamide-purged autologous BMT for ALL or AML. rHuEPO was administered intravenously at a dose of 75 U/kg/day for 30 days after transplant. Ten rHuEPO-treated patients receiving allogeneic BMT and 10 given autologous BMT were compared with 15 allogeneic and 10 autologous historical controls. Endogenous EPO production was appropriate for the degree of anemia after autologous BMT. In these patients, rHuEPO did not accelerate erythroid repopulation and did not modify transfusion requirements. With allogeneic BMT, erythroid marrow activity increased faster in patients given rHuEPO than in controls and resulted in higher red cell production, the mean reticulocyte count on day +30 being 187 +/- 51 x 10(9)/l in treated patients versus 107 +/- 63 x 10(9)/l in controls (p < 0.01). The total number of RBC units administered was 1.7 +/- 1.3 in the rHuEPO group versus 5.1 +/- 3.0 in the control group (p < 0.001). The total number of platelet transfusions was 4.0 +/- 2.3 for patients given allogeneic BMT and receiving rHuEPO versus 8.4 +/- 6.8 for historical controls (p < 0.05) whereas it was similar in rHuEPO-treated and control autologous BMT patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1994

Busulfan, cyclophosphamide and melphalan as conditioning regimen for bone marrow transplantation in children with myelodysplastic syndromes.

As typical disorders of the elderly, myelodysplastic syndromes (MDSs) are relatively unusual in childhood. Nevertheless, up to 17% of cases of pediatric acute myeloid leukemia may have a preleukemic phase. In young patients, the goal of treatment is eradication of the preleukemic malignant clone and reconstitution of normal hematopoiesis. Allogeneic bone marrow transplantation (BMT) has proved to be capable of this, but the optimal conditioning treatment to achieve eradication remains to be defined. Between May 1989 and June 1993, eight consecutive pediatric patients with MDS received a marrow transplant from an HLA-identical, mixed lymphocyte culture (MLC) non-reactive sibling. Diagnosis at time of presentation was refractory anemia with excess of blasts (RAEB) in two patients, RAEB in transformation (RAEB-t) in three, and juvenile chronic myelogenous leukemia (JCML, the pediatric counterpart of adult chronic myelomonocytic leukemia) in the remaining three children. Conditioning regimen consisted of busulfan, cyclophosphamide and melphalan, three alkylating agents potentially capable of killing also dormant preleukemic stem cells. The preparative regimen was very well tolerated, and all patients engrafted promptly. Six out of eight patients (75%) are alive and well with a median observation time of 20 months (range 8-34 months). Serial karyotype monitoring and molecular analyses have demonstrated a full chimerism of donor cells and the complete disappearance of trisomy 8 detected before transplant in three cases. All surviving patients have a Karnofsky score of 100%. One boy, affected by RAEB-t with monosomy 7 resistant to treatment with low-dose ara-C, relapsed 11 months after BMT, evolved in AML and died from progressive leukemia. Another patient with RAEB died on day +95 after BMT due to interstitial pneumonia of unclear etiology. This study confirms that allogeneic BMT is the treatment of choice in pediatric patients with MDS, and suggests that the employed conditioning regimen is a safe and effective means for eradicating the preleukemic malignant clone. Particularly noteworthy is that the three children with JCML obtained a complete remission and one of them is now a long-term survivor.

Adolescent↗

PubMed1993

Disposition of high-dose busulfan in pediatric patients undergoing bone marrow transplantation.

We studied the pharmacokinetics of busulfan (16 mg/kg) in 16 pediatric patients affected by malignant and nonmalignant disorders between 6 months and 19 years of age (mean +/- SD, 5.7 +/- 6.5 years) who were undergoing allogenic (15 patients) and autologous (one patient) bone marrow transplantation. In all children, the conditioning regimen consisted of busulfan given orally at a dose of 1 mg/kg every 6 hours for 16 doses (total dose, 16 mg/kg), associated with other drugs. The pharmacokinetics of busulfan was studied during the 6-hour dosing interval on the third day of therapy by use of a high-performance liquid chromatographic assay. The value for the time to reach maximum concentration, expressed as mean +/- SD, was 1.1 +/- 0.5 hour; maximum concentration was 609.6 +/- 225.3 ng/ml; steady-state concentration was 358.9 +/- 135.5 ng/ml; area under the plasma concentration-time curve was 2153.6 +/- 813.1 ng.hr/ml; oral clearance was 0.535 +/- 0.226 L/hr/kg; and half-life was 2.4 +/- 0.8 hours. Age-related differences in busulfan disposition were observed. The mean busulfan oral clearance in a group of 10 patients with an age range from 6 months to 3 years was 0.619 L/hr/kg, whereas six patients whose ages ranged from 7 to 19 years had a oral clearance of 0.396 L/hr/kg. The half-lives for busulfan during infancy decrease continuously until early childhood but were prolonged in older children. No significant relationship between systemic exposure to busulfan and drug effect was observed.

Administration, Oral↗

PubMed1993

Accelerated erythroid repopulation with no stem-cell competition effect in children treated with recombinant human erythropoietin after allogeneic bone marrow transplantation.

We carried out a pilot study on the use of recombinant human erythropoietin (rHuEPO) to accelerate erythropoietic engraftment in paediatric patients undergoing allogeneic BMT. rHuEPO was administered intravenously at a dose of 75 U/kg per day for 30 d after transplant. Erythroid repopulation, evaluated sequentially through the serum transferrin receptor, was faster in 15 patients receiving rHuEPO than in 16 historical controls (P = 0.0003). This faster erythroid engraftment resulted in a reduction in the total number of red blood cell units required to reach transfusion independence (2.7 +/- 1.2 v 4.2 +/- 2.3, P = 0.027). No significant difference in leucocyte or platelet regeneration was observed. These findings indicate that rHuEPO administration can accelerate erythroid recovery after allogeneic BMT and reduce red cell transfusion requirements with no stem-cell competition effect.

Adolescent↗

PubMed1993

Growth in children after bone marrow transplantation.

Growth velocity pattern and growth hormone (GH) secretion were evaluated in 18 prepubertal patients (13 males, 5 females), receiving an allogeneic (7 patients) or autologous (11 patients) bone marrow transplantation (BMT). Children were affected by oncological or hematological malignancies and the age range was between 2 and 11 years. Nine patients received a conditioning regimen consisting of chemotherapy and fractionated total body irradiation (TBI) (12 Gy in 6 fractions over 3 days), whereas 9 children also received previous prophylactic cranial irradiation during first-line chemotherapy. GH secretion in response to pharmacological stimuli (insulin, arginine and/or L-Dopa) was evaluated when growth failure occurred. The 9 prepubertal patients who had received previous prophylactic cranial irradiation during first-line chemotherapy, showed a significant decrease in growth rate already 1 year after BMT and this reduced growth rate presented a progressive further decrease in the 2nd and 3rd year after BMT. On the contrary, in the 9 prepubertal children treated with TBI and chemotherapy alone, growth rate presented an impressive decrease only during the 3rd year. In the two groups of patients, pretransplantation growth rates were comparable, while, due to the earlier growth failure in children receiving TBI and previous prophylactic cranial irradiation, mean standard deviation score (SDS) significantly differed at 1 and 2 years following BMT. Such a difference disappeared at 3 years after BMT, because of the late decrease in growth rate in patients given TBI and chemotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton↗