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Biomedical subjects

F Locatelli

Publications and source records attributed to F Locatelli.

At least 181 records · Page 10Linked to original sources
PubMed1999

Total body irradiation, thiotepa, and cyclophosphamide as a conditioning regimen for children with acute lymphoblastic leukemia in first or second remission undergoing bone marrow transplantation with HLA-identical siblings.

PURPOSE: Allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA-identical siblings can be used to treat children with acute lymphoblastic leukemia (ALL). However, a significant proportion of patients with ALL who undergo HSCT relapse. For this reason, we prospectively evaluated a preparative regimen that included total body irradiation (TBI), thiotepa (TT), and cyclophosphamide (CY) in patients with high-risk ALL in first complete remission (CR) and in children with ALL in second CR. PATIENTS AND METHODS: Forty children (median age, 9 years; range, 1 to 18 years) with ALL in first or second CR who underwent allogeneic HSCT from HLA-identical siblings were conditioned with a combination of fractionated TBI, TT (10 mg/kg), and CY (120 mg/kg over 2 days). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine administered intravenously at a dose of 1 to 3 mg/kg/d for the first 21 days and subsequently orally at a dose of 6 mg/kg/d. RESULTS: All assessable patients were engrafted, with a median time of 11 and 24 days for neutrophil and platelet recovery, respectively. The preparative regimen was well tolerated. Only one patient died as a result of regimen-related causes. Eight patients relapsed at a median time of 8 months after transplantation (range, 3 to 9 months), and this determined a cumulative probability of relapse of 23%. Twenty-six of 40 patients (65%) are alive and in complete hematologic remission, with a median observation time of 36 months (range, 14 to 57 months), which results in a disease-free survival (DFS) at 3 years of 65%. The 13 patients who underwent transplantation in first CR had a DFS of 85%, whereas the 27 patients who underwent HSCT in second CR had a DFS of 56%. CONCLUSION: These data suggest that TT is an effective cytotoxic drug that can be safely added to the classical TBI-CY regimen. Because of its cell cycle-independent action, good CNS diffusion, and limited extramedullary toxicity, TT may contribute to increasing the percentage of children with ALL who are successfully cured with allogeneic BMT.

Adolescent↗
PubMed1999

Cause-specific mortality in type 2 diabetes. The Verona Diabetes Study.

OBJECTIVE: This population-based study, carried out in the framework of the Verona Diabetes Study, investigated mortality from specific causes in known type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A cohort of 7,148 known type 2 diabetic patients (3,366 men and 3,782 women) was identified on 31 December 1986 and followed up for 5 years (1987-1991). Underlying causes of death were obtained from death certificates and were coded according to the International Classification of Diseases, Ninth Revision. Cause-specific death rates of diabetic subjects were compared with those of the inhabitants of Verona. By 31 December 1991, 1,550 diabetic subjects (744 men and 806 women) had died. RESULTS: The standardized mortality ratio (SMR) for all causes of death was 1.42 (95% CI 1.35-1.50). The highest SMRs were for the following specific causes: diabetes (SMR 4.47 [3.91-5.10]), gastrointestinal diseases (1.83 [1.50-2.21])--particularly liver cirrhosis (2.52 [1.96-3.20])--and cardiovascular diseases (1.34 [1.23-1.44]), particularly cerebrovascular (1.48 [1.25-1.73]) and ischemic heart diseases (1.41 [1.24-1.62]). A significantly higher than expected risk of mortality for cardiovascular causes was already present in the first 5 years after diagnosis and decreased with age. Type 2 diabetic patients treated with insulin had a higher risk of dying than those treated orally or by diet. CONCLUSIONS: The highest SMRs in the diabetic cohort were for diabetes and liver cirrhosis. The mortality risk for cardiovascular diseases, although significantly higher than expected, was much lower in Italian type 2 diabetic patients than that reported for American patients. The evidence of an early effect on mortality suggests that prevention, early diagnosis, and treatment should be improved.

Age Factors↗
PubMed1999

Feasibility and safety of a new technique of extracorporeal photochemotherapy: experience of 240 procedures.

BACKGROUND AND OBJECTIVE: Extracorporeal photochemotherapy (ECP) is a therapeutic approach based on the biological effects of ultraviolet light (UV) - A and psoralens on mononuclear cells collected by apheresis. Recently, ECP has been under investigation as an alternative treatment for various immune and autoimmune diseases. The aim of this study was to evaluate the safety and feasibility of a new three-step ECP technique, in terms of reproducibility, acceptance, tolerability, and short and long term side effects. DESIGN AND METHODS: Seventeen patients affected by acute or chronic graft-versus-host disease (GvHD), pemphigus vulgaris, or interferon-resistant chronic hepatitis C and one patient being treated for prevention of heart transplant rejection underwent 240 ECP procedures. MNC collection and processing parameters were recorded, biological effects of UV-A/8 methoxy-psoralen (8-MOP) were evaluated, and short and long term side effects were monitored. RESULTS: At a mean follow up of 7 months (range 2-19) 240 ECP had been completed, a mean of 7,136 mL (range 1,998-10,591) of whole blood having beenprocessed per procedure. The mean of total nucleated cells collected per procedure was 6.5x109 (range 0.65-23.8), with a mean MNC percentage of 85% (41. 4-98%) in a mean final volume of 115.5 mL (37-160). No severe side effects were documented and no infectious episodes occurred throughout the course of the treatment. INTERPRETATION AND CONCLUSIONS: The new ECP technique was highly reproducible as regards the collection and each processing step. Short and long term side effects were mild. No increase in infectious episodes was recorded. All patients willingly underwent ECP, demonstrating an excellent tolerability for the procedure even after several courses.

Adolescent↗
PubMed1999

Mobilization and selection of peripheral blood hematopoietic progenitors in children with systemic sclerosis.

BACKGROUND AND OBJECTIVE: Autologous transplant of lymphocyte-depleted peripheral blood stem cells has been proposed for treatment of patients with severe autoimmune disease. However, until now, no data are available on the safety and feasibility of both stem cell collection and selection in pediatric patients with these disorders. We report on three children affected by systemic sclerosis with lung involvement, who received chemotherapy and granulocyte colony-stimulating factor (G-CSF) to mobilize autologous peripheral blood progenitors. DESIGN AND METHODS: The priming regimen consisted of cyclophosphamide (CY, 4 g/m(2)) and G-CSF (lenograstim, 10 microg/kg/day starting 2 days after cyclophosphamide administration until stem cell collection). Leukapheresis was performed when WBC and CD34+ cell count were at least 2 x 10(9)/L and 0.03 x 10(9)/L, respectively. In the first patient, positive selection of CD34+ cells was performed through the Ceprate SC stem cell concentrator (CellPro, Bothell, WA, USA). In the remaining 2 children, progenitor cells were also purged with negative selection of CD4+ and CD8+ lymphocytes performed by means of the Isolex 300i device (Baxter). RESULTS: All patients tolerated the priming regimen well and did not present any sign of autoimmune disease exacerbation. Collection was successful in all children and the number of CD34+ cells before selection ranged between 10.7 x 10(6) and 17.6 x 10(6)/kg of patient body weight. The selection of haematopoietic stem cells in the 3 patients resulted in at least 2. 6-log T-cell depletion of the cell content, with a recovery of the initial value of CD34+ cells comprised between 21 and 44%. After, a preparative regimen consisting of CY (200 mg/kg over 4 days) and Campath-1 G in vivo (10 mg/day for 2 consecutive days), patients were transplanted using cryopreserved lymphocyte-depleted progenitor cells. In all cases, a prompt hematopoietic engraftment was observed. INTERPRETATION AND CONCLUSIONS: Taken together these data suggest that mobilization, collection and selection of hematopoietic progenitors are safe and feasible in children with autoimmune disease.

Autoimmune Diseases↗
PubMed1999

Cell therapy: achievements and perspectives.

BACKGROUND AND OBJECTIVE: Cell therapy can be considered as a strategy aimed at replacing, repairing, or enhancing the biological function of a damaged tissue or system by means of autologous or allogeneic cells. There have been major advances in this field in the last few years. This has prompted the Working Group on Hematopoietic Cells to examine the current utilization of this therapy in clinical hematology. EVIDENCE AND INFORMATION SOURCES: The method employed for preparing this review was that of informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the single points in order to reach an agreement on different opinions and eventually approved the final manuscript. Some of the authors of the present review have been working in the field of cell therapy and have contributed original papers in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. STATE OF THE ART: Lymphokine-activated killer (LAK) and tumor-infiltrating lymphocytes (TIL) have been used since the '70s mainly in end-stage patients with solid tumors, but the clinical benefits of these treatments has not been clearly documented. TIL are more specific and potent cytotoxic effectors than LAK, but only in few patients (mainly in those with solid tumors such as melanoma and glioblastoma) can their clinical use be considered potentially useful. Adoptive immunotherapy with donor lymphocyte infusions has proved to be effective, particularly in patients with chronic myeloid leukemia, in restoring a state of hematologic remission after leukemia relapse occurring following an allograft. The infusion of donor T-cells can also have a role in the treatment of patients with Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disorders. However, in this regard, generation and infusion of donor-derived, virus specific T-cell lines or clones represents a more sophisticated and safer approach for treatment of viral complications occurring in immunocompromised patients. Whereas too few clinical trials have been performed so far to draw any firm conclusion, based on animal studies dendritic cell-based immunotherapy holds promises of exerting an effective anti-tumor activity. Despite leukemic cells not being immunogenic, induction on their surface of co-stimulatory molecules or generation of leukemic dendritic cells may induce antileukemic cytotoxic T-cell responses. Tumor cells express a variety of antigens and can be genetically manipulated to become immunogenic. The main in vitro and in vivo functional characteristics of marrow mesenchymal stem cells (MSCs) with particular emphasis on their hematopoietic regulatory role are reviewed. In addition, prerequisites for clinical applications using culture-expanded mesenchymal cells are discussed PERSPECTIVES: The opportuneness of using LAK cells or activated natural killer (NK) cells in hematologic patients with low tumor burden (e.g. after stem cell transplantation) should be further explored. Moreover the role of new cytokines in enhancing the antineoplastic activity of NK cells and the infusion of selected NK in alternative to CTL for graft versus leukemia (GVL) disease (avoiding graft versus host disease (GvHD) seems very promising. Separation of GVL from GvHD through generation and infusion of leukemia-specific T-cell clones or lines is one of the most intriguing and promising fields of investigations for the future. Likewise, strategies devised to improve immune-reconstitution and restore specific anti-infectious functions through either induction of unresponsiveness to recipient alloantigens or removal of alloreactive donor T-cells might increase the applicability and success of hematopoietic stem cell transplantation. (ABSTRACT TRUNCATED)

Animals↗
PubMed1998

Early treatment of acute graft-versus-host disease with high- or low-dose 6-methylprednisolone: a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation.

Ninety-five patients undergoing an allogeneic bone marrow transplant (BMT) and developing acute graft-versus-host disease (aGvHD) were randomized to receive low-dose intravenous 6-methylprednisolone (6MPred; 2 mg/kg /d; n = 47) or high-dose 6MPred (10 mg/kg/d; n = 48) for 5 days, with subsequent tapering doses. On day 5 patients not responding or progressing on low-dose 6MPred could be switched to high-dose 6MPred. All patients, aged 1 to 55 years, were recipients of unmanipulated BMT from HLA identical sibling donors. Patients were stratified at randomization for age (</>/= 20 years), disease (acute leukemia, chronic myeloid leukemia [CML], nonneoplastic disease), disease status (early/advanced), and GvHD prophylaxis (cyclosporin/cyclosporin + methotrexate). Primary endpoints were response to treatment and evolution of aGvHD to grade III-IV. Secondary endpoints were cytomegalovirus (CMV) infections, transplant-related mortality (TRM), and relapse. The median interval between BMT and treatment was 12 days (6 to 43). Results in the two groups (2 v 10 mg/kg) were as follows: response of aGvHD 68% versus 71% (P = .9), evolution to aGvHD grade III-IV 17% versus 20% (P = . 6), CMV infections 55% versus 60% (P = .7), 3-year actuarial TRM 28% versus 32% (P = .7), relapse 17% versus 7% (P = .1). The actuarial survival at 3 years was 63% versus 62% (P = .9) with a median follow up of 580 and 778 days. On day 5 of therapy, 26 patients assigned to low-dose (2 mg/kg) 6MPred were switched to a higher dose of 6MPred because of no response or progression. Their actuarial TRM was 46%, which is significantly higher than TRM of patients who responded on 2 mg/kg and continued with tapering doses (TRM = 16%, P = .007). In conclusion, early treatment of acute GvHD with 6MPred 10 mg/kg/d does not improve the response rate as compared with 2 mg/kg/d, nor does it prevent evolution to aGvHD grade III-IV. CMV infections, TRM, and survival were also comparable. A group of patients at high risk of TRM can be identified after 5 days of treatment with 6MPred 2 mg/kg and could be eligible for alternative forms of therapy.

Actuarial Analysis↗
PubMed1998

Kappa-B like DNA-binding activity is enhanced after spaced training that induces long-term memory in the crab Chasmagnathus.

Regulation of gene expression has been involved in long-term memory consolidation. Present results support the role of Rel/ NFkappa-B like activation in this process. In the crab Chasmagnathus, the spaced presentation of 15 or more danger stimuli induces long-term habituation (LTH), while no LTH is observed after a massed training of 600 trials. When a group trained with 30 spaced trials was compared with a passive control group and massed trained groups, a higher level of specific Rel/kappa-B like DNA-binding activity was found in brain nuclear extracts. These results strongly suggest that the enhancement of Rel/kappa-B like DNA-binding activity in the brain is specifically related to LTH formation.

Animals↗
PubMed1998

Evaluation of growth hormone bioactivity using the Nb2 cell bioassay in children with growth disorders.

The Nb2 cell bioassay could be a useful tool for evaluating human growth hormone (hGH) bioactivity, but is not specific for hGH since it relies on the ability of the hormone to produce effects by cross-reacting with the lactogenic receptor on Nb2 cells. We studied the biological activity of both endogenous and exogenous hGH in short patients using the Nb2 bioassay after inhibiting the mitogenic effect of the other lactogenic hormone, that is human prolactin (hPRL), by adding a specific antibody against hPRL to each assay. The in vitro study showed a significant (p<0.0001) increase in Nb2 cell proliferation when increasing concentrations of highly purified hGH were added to the cell culture. A complete inhibition of Nb2 cell replication was observed after adding a specific antibody against hGH. The in vivo study showed a significantly (p<0.0001) lower hGH bioactivity (4.90+/-0.28 ng/ml) evaluated during stimulation tests in 9 children with total idiopathic GH deficiency, mean age 9.25+/-1.99 years, in comparison with that found in 11 short children with normal growth velocity, mean age 8.22+/-1.41 years (12.25+/-1.19 ng/ml). Likewise, serum GH levels measured by immunofluorometric assay IFMA in the same serum samples were significantly (p<0.001) lower in the 9 GH-deficient (1.97+/-0.37 ng/ml) than in the 11 short children (21.85+/-2.71 ng/ml). Moreover, we evaluated GH concentrations using both IFMA and the Nb2 cell bioassay in serum samples collected from another 11 idiopathic GH-deficient children, mean age 10.71+/-1.18 years, before and then, 6 and 24 hours following the 1 st injection of r-hGH (0.1 IU/kg sc). Serum GH values measured by both IFMA and Nb2 bioassay significantly (p<0.0001) increased 6 hours after r-hGH administration and decreased to reach basal levels after 24 hours. In conclusion, the Nb2 cell bioassay with minor modifications seems to provide a specific and sensitive assessment of hGH bioactivity.

Animals↗
PubMed1998

Recommendations on the use of colony-stimulating factors in children: conclusions of a European panel.

UNLABELLED: During 1996 and 1997 a panel of European haematologists, oncologists, and neonatologists developed specific paediatric guidelines for the use of colony stimulating factors based on published literature and the clinical experience of these specialists within each of 13 countries. Well established indications for use comprise intervention in patients with life-threatening infection, adjunctive therapy post autologous bone marrow transplantation (BMT), mobilization of peripheral blood progenitor cells for autologous BMT, patients with acquired aplastic anaemia on anti-lymphocyte globulin and cyclosporin regimen, and severe congenital neutropenia. Less clear indications include primary prophylaxis to support dose intensification in children with high risk/advanced malignancies, secondary prophylaxis to prevent neutropenia in patients with a history of severe neutropenia, support therapy in cases of poor marrow function following BMT and for deteriorating marrow function following successful BMT, in neonatal sepsis and non infectious neonatal neutropenia, in drug induced neutropenia and in HIV-positive patients. Treatment is generally well tolerated and granulocyte colony stimulating factor appears better tolerated than granulocyte and macrophage colony stimulating factor. Economically colony stimulating factors have not been shown to induce excessive costs for a given patient. CONCLUSION: In general the adult guidelines are applicable to children but additional considerations (aggressive or very progressive childhood neoplasms, specific indications, neonatal use, congenital disorders) must be taken into account.

Bone Marrow Transplantation↗
PubMed1998

Isoniazid-induced pure red cell aplasia in two siblings.

Pure red cell aplasia (PRCA) is a rare complication of treatment with isoniazid mainly observed in adults. We report two siblings who had anemia caused by PRCA during administration of isoniazid. On discontinuation of isoniazid, the anemia resolved rapidly. PRCA should be considered as a possible cause of unexplained anemia during isoniazid therapy in children.

Antitubercular Agents↗
PubMed1998

Immunization with Haemophilus influenzae type b conjugate vaccine in children given bone marrow transplantation: comparison with healthy age-matched controls.

Forty-seven patients (age range, 7 months-18 years) with malignant (38 cases) and nonmalignant (9 cases) disorders given an allogeneic or an autologous bone marrow transplantation (BMT) were immunized with Haemophilus influenzae type b (Hib) polysaccharide-diphtheria toxoid conjugate vaccine administered in a single dose at different time points after transplantation. Results were compared with those of 13 healthy children matched for age and sex who received the same immunization schedule. Serum and saliva samples for measurement of total IgG subclass and specific antibody levels were obtained from patients and healthy controls before and 3 weeks after vaccination. Twenty-five of the 47 patients (53%) had a specific anti-Hib IgG response, while an effective IgA and IgM response was mounted by 23 (49%) and 11 (23%) children, respectively. In the control group, 13 of 13 subjects mounted a specific IgG antibody production (P < 0.005 in comparison to the patients' response rate), while an IgA and IgM response was demonstrated in 12 (92%; P < 0.01 compared to transplanted patients) and 7 (54%; P < 0.05 in comparison to BMT recipients) children, respectively. Lapse of time from BMT to immunization was the most important factor predicting antibody response, as proved by an effective increase in prevaccination specific IgG levels in the majority of patients vaccinated after 2 years from transplant. Our data demonstrate that BMT recipients have a reduced capacity to mount an antibody response to polysaccharide antigens compared to normal controls, even when a protein-conjugated vaccine is employed. Since time after transplant is the major factor influencing the recovery of immune reactivity to polysaccharide antigens, the ontogeny of the B cell repertoire seems to follow a predetermined sequential program of development.

Adolescent↗
PubMed1998

Immunotherapy with low-dose recombinant interleukin 2 after high-dose chemotherapy and autologous stem cell transplantation in neuroblastoma.

The purpose of this study was to evaluate in a phase I-II trial whether low doses of recombinant human interleukin 2 (rHuIL-2) over a prolonged period of time are safe and effective in eradicating or controlling minimal residual disease in children with neuroblastoma given high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). From January 1992 to July 1996, 17 consecutive patients, with either stage IV or relapsed neuroblastoma, were enrolled. Patients received rHuIL-2 after a median time interval (min-max) of 105 days (56-153) after HDCT and ASCT. The protocol consisted of 2 'priming' courses of rHuIL-2 at escalating doses administered intravenously at 72-h intervals, followed by 'maintenance' with 11 monthly and six bimonthly boosting 5-day courses administered subcutaneously on an outpatient basis. At April 1997, 7 out of the 17 patients had completed the treatment schedule, four had discontinued treatment because of toxicity and four because of relapse; the remaining two patients are still on treatment, having completed 15 courses. Expansion of T lymphocytes, together with an increase in both natural killer cells and in activated T lymphocytes was evidenced. After a median (min-max) follow-up time of 30 (16-64) months, 12 out of 17 patients are alive and well. Two patients relapsed and died 14 and 35 months after transplant. Three patients are alive after having relapsed at 41, 21 and 13 months. The actuarial 2-year event-free survival and overall survival are 67% and 92% respectively. Intermittent administration of low doses of rHuIL-2 given for a long period of time is well tolerated and seems capable of controlling minimal residual disease after HDCT and ASCT in children with high-risk neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Autologous bone marrow transplantation for treatment of isolated central nervous system relapse of childhood acute lymphoblastic leukemia. AIEOP/FONOP-TMO group. Associzione Italiana Emato-Oncologia Pediatrica.

The purpose of this study was to assess the role of ABMT in children with ALL who are in 2nd CR after an early isolated CNS relapse. All children experiencing an isolated CNS relapse at 10 AIEOP centers (Associazione Italiana Emato-Oncologia Pediatrica) from 1986 to 1992 were eligible for this study. The series included 69 patients who relapsed within 3 years from diagnosis: 19 underwent ABMT, nine patients underwent ALLO-BMT from an HLA-identical sibling, and 41 received conventional chemotherapy (CHEMO). Statistical analysis was performed using a Cox's regression model, adjusting for the waiting time before transplantation and prognostic factors. The 5 years DFS was 56.3% (s.e. 12.3) for patients in the ABMT group. This compared favorably with the poor result (12.6% (s.e. 5.9)) seen in the CHEMO group. The risk of failures was reduced by one-third in the ABMT group as compared to the CHEMO group in the multivariate analysis (P < 0.01). In the ALLO group four out of nine patients were in CCR 4-5 years post-transplant. This study suggests that ABMT may also represent a valuable therapeutic choice for patients lacking a matched familiar donor in 2nd CR after an early isolated CNS relapse.

Adolescent↗
PubMed1998

G-CSF administration following peripheral blood progenitor cell (PBPC) autograft in lymphoid malignancies: evidence for clinical benefits and reduction of treatment costs.

Clinical value and costs of G-CSF administration following autograft with mobilized peripheral blood progenitor cells (PBPC) were evaluated in two sequential groups of 20 patients each, treated for lymphoid neoplasms in the period February 1993 to January 1996. One group was given G-CSF (Filgrastim) (5 microg/kg/day), starting on day +1 until ANC was > 500/microl, the other received no G-CSF. All patients were conditioned with mitoxantrone 60 mg/m2 + L-PAM 180 mg/m2 and received large numbers of PBPC (median of 12 and 13 x 10(6) CD34+/kg, respectively). The median time to ANC > 500/microl was 10 days in the G-CSF group vs 14 days in controls (P < 0.0001). G-CSF was associated with a slightly faster platelet recovery (11 vs 13 days to plts > 20000/microl, P = 0.09). Median duration of fever (2.5 vs 5 days, P = 0.028), nonprophylactic antibiotics (8 vs 11 days, P = 0.019), and post-transplant hospitalization (13 vs 16 days, P = 0.0028) were also significantly reduced. The average cost per treatment in the G-CSF group amounted to about US$18241 as compared to US$21868 in the control group, implying a cost reduction of approximately 16%. Thus, G-CSF reduced morbidity with cost containment, supporting its use even if autograft is performed with large quantities of PBPC.

Adolescent↗
PubMed1998

Autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in Italy. AIEOP/FONOP-TMO Group. Italian Association of Paediatric Haemato-Oncology.

From January 1984 to December 1994, ABMT was performed on 154 children (101 males, 53 females; median age 10, range 3-21 years) with ALL and registered for BMT by the AIEOP (Italian Association of Paediatric Haemato-Oncology). All patients were in CR: 98 were in 2nd CR and 56 were in >2nd CR. Fifteen children (9.7%) died of transplant-related mortality. Ninety-five patients (61.6%) relapsed at a median of 5 (range 1-42) months after ABMT. The 8-year EFS according to pre-BMT status was 34.6% (s.e. 4.9) for 2nd CR patients and 10.6% (s.e. 5.6) for patients in >2nd CR. By univariate analysis, site of relapse (isolated extramedullary (IE) vs BM: EFS = 68.5% vs 18.2%; P < 0.0001) and TBI containing regimen (TBI vs no TBI: EFS = 48.1 vs 15.4%; P = 0.0023) were significant factors for 2nd CR patients. When the 2nd CR subset with BM involvement was analysed, TBI became insignificant (EFS = 25.4 vs 11.8%). No factors influenced EFS in patients in >2nd CR. By multivariate analysis, site of relapse was the only significant factor in 2nd CR patients (P < 0.0001). In conclusion, ABMT is an effective treatment after one early IE relapse. Few patients can be rescued after BM relapse.

Adolescent↗