Acute chest syndrome in children with sickle cell disease: Data from a national AIEOP cohort identify priority areas of intervention in a hub-and-spoke system.

Acute chest syndrome (ACS) is a frequent cause of hospitalization in sickle cell disease (SCD). Despite advances in acute care, many settings still lack knowledge about ACS best practices. After the AIEOP Guidelines were published in 2012, suggesting standardized management in Italy, a retrospective study was performed to assess the diagnostic and therapeutic pathways of ACS in children. From 2013 to 2018, 208 ACS episodes were presented by 122/583 kids in 11 centres. 73 were male, mean age 10.9 years, 85% African, 92% HbSS or Sß°. In our hub-and-spoke system, a good adherence to Guidelines was documented, but discrepancies between reference centres and general hospitals were noted. Improvement is needed for timely transfer to reference centres, use of incentive spirometry, oxygen therapy and pain management.

Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP).

Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3 per million population per year in the Western world, but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.

A Case Series and Literature Review of Isavuconazole Use in Pediatric Patients with Hemato-oncologic Diseases and Hematopoietic Stem Cell Transplantation.

We analyzed the use of isavuconazole (ISA) as treatment or prophylaxis for invasive fungal disease (IFD) in children with hemato-oncologic diseases. A multicentric retrospective analysis was performed among centers belonging to the Italian Association for Pediatric Hematology and Oncology (AIEOP). Pharmacokinetic (PK) monitoring was applied by a high-performance liquid chromatography-tandem mass spectrometry (HLPC-MS/MS) assay. Twenty-nine patients were studied: 10 during chemotherapy and 19 after allogeneic hematopoietic stem cell transplantation (HSCT). The patients consisted of 20 males and 9 females with a median age of 14.5 years (age range, 3 to 18 years) and a median body weight of 47 kg (body weight range, 15 to 80 kg). ISA was used as prophylaxis in 5 patients and as treatment in 24 cases (20 after therapeutic failure, 4 as first-line therapy). According to European Organization for Research and Treatment of Cancer (EORTC) criteria, we registered 5 patients with proven IFD, 9 patients with probable IFD, and 10 patients with possible IFD. Patients with a body weight of <30 kg received half the ISA dose; the others received ISA on the adult schedule (a 200-mg loading dose every 8 h on days 1 and 2 and a 200-mg/day maintenance dose); for all but 10 patients, the route of administration switched from the intravenous route to the oral route during treatment. ISA was administered for a median of 75.5 days (range, 6 to 523 days). The overall response rate was 70.8%; 12 patients with IFD achieved complete remission, 5 achieved partial remission, 5 achieved progression, and 3 achieved stable IFD. No breakthrough infections were registered. PK monitoring of 17 patients revealed a median ISA steady-state trough concentration of 4.91 mg/liter (range, 2.15 to 8.54 mg/liter) and a concentration/dose (in kilograms) ratio of 1.13 (range, 0.47 to 3.42). Determination of the 12-h PK profile was performed in 6 cases. The median area under the concentration-time curve from 0 to 12 h was 153.16 mg·h/liter (range, 86.31 to 169.45 mg·h/liter). Common Terminology Criteria for Adverse Events grade 1 to 3 toxicity (increased transaminase and/or creatinine levels) was observed in 6 patients, with no drug-drug interactions being seen in patients receiving immunosuppressants. Isavuconazole may be useful and safe in children with hemato-oncologic diseases, even in the HSCT setting. Prospective studies are warranted.

Pharmacogenetics and induction/consolidation therapy toxicities in acute lymphoblastic leukemia patients treated with AIEOP-BFM ALL 2000 protocol.

Drug-related toxicities represent an important clinical concern in chemotherapy, genetic variants could help tailoring treatment to patient. A pharmacogenetic multicentric study was performed on 508 pediatric acute lymphoblastic leukemia patients treated with AIEOP-BFM 2000 protocol: 28 variants were genotyped by VeraCode and Taqman technologies, deletions of GST-M1 and GST-T1 by multiplex PCR. Toxicities were derived from a central database: 251 patients (49.4%) experienced at least one gastrointestinal (GI) or hepatic (HEP) or neurological (NEU) grade III/IV episode during the remission induction phase: GI occurred in 63 patients (12.4%); HEP in 204 (40.2%) and NEU in 44 (8.7%). Logistic regression model adjusted for sex, risk and treatment phase revealed that ITPA rs1127354 homozygous mutated patients showed an increased risk of severe GI and NEU. ABCC1 rs246240 and ADORA2A rs2236624 homozygous mutated genotypes were associated to NEU and HEP, respectively. These three variants could be putative predictive markers for chemotherapy-related toxicities in AIEOP-BFM protocols.

Acquisition of C3d-Binding Activity by De Novo Donor-Specific HLA Antibodies Correlates With Graft Loss in Nonsensitized Pediatric Kidney Recipients.

Alloantibody-mediated graft injury is a major cause of kidney dysfunction and loss. The complement-binding ability of de novo donor-specific antibodies (dnDSAs) has been suggested as a prognostic tool to stratify patients for clinical risk. In this study, we analyzed posttransplant kinetics of complement-fixing dnDSAs and their role in antibody-mediated rejection development and graft loss. A total of 114 pediatric nonsensitized recipients of first kidney allograft were periodically monitored for dnDSAs using flow bead assays, followed by C3d and C1q assay in case of positivity. Overall, 39 patients developed dnDSAs, which were C1q(+) and C3d(+) in 25 and nine patients, respectively. At follow-up, progressive acquisition over time of dnDSA C1q and C3d binding ability, within the same antigenic specificity, was observed, paralleled by an increase in mean fluorescence intensity that correlated with clinical outcome. C3d-fixing dnDSAs were better fit to stratify graft loss risk when the different dnDSA categories were evaluated in combined models because the 10-year graft survival probability was lower in patients with C3d-binding dnDSA than in those without dnDSAs or with C1q(+) /C3d(-) or non-complement-binding dnDSAs (40% vs. 94%, 100%, and 100%, respectively). Based on the kinetics profile, we favor dnDSA removal or modulation at first confirmed positivity, with treatment intensification guided by dnDSA biological characteristics.

Gonadal and uterine function in female survivors treated by chemotherapy, radiotherapy, and/or bone marrow transplantation for childhood malignant and non-malignant diseases.

OBJECTIVE: To evaluate gonadal function and uterine volume in a cohort of female survivors treated by chemotherapy, radiotherapy, and/or stem cell transplantation (SCT) for childhood malignant and non-malignant diseases. DESIGN: An observational study. SETTING: S. Matteo Hospital, Pavia, Italy. POPULATION: A cohort of 135 female survivors. METHODS: A clinical, hormonal, and ultrasonographic evaluation. Thirty-three patients (24%) had non-malignant haematologic diseases (thalassaemia or sickle cell anaemia), 68 (50%) had leukaemia, 23 (17%) had lymphomas, and 11 (8%) had solid tumours. In total, 106 patients had received SCT, preceded by a conditioning regimen. MAIN OUTCOME MEASURES: Anti-Müllerian hormone (AMH) and Inhibin-B, and uterine volume. RESULTS: The median concentrations of AMH and Inhibin-B in the entire cohort were 0.12 ng/ml (interquartile range, IQR, 0.1-0.5 ng/ml) and 3.5 pg/ml (IQR 0.1-13.2 pg/ml), respectively. In a stepwise ordered logistic regression analysis, conventional chemotherapy for the treatment of malignancies, as opposed to total body irradiation (TBI), was the only oncologically significant predictor of increased AMH levels (OR 4.8, 95% CI 1.9-12, P < 0.001). Conditioning treatment before or after menarche did not influence AMH concentrations (P = 0.24). The best predictor of reduced uterine volume was TBI during the preparation for the allograft (OR 3.5, 95% CI 1.4-8.4, P = 0.006). Increasing age at treatment (OR 0.86, 95% CI 0.77-0.95, P = 0.04), chemotherapy, as opposed to other treatments (OR 0.09, 95% CI 0.03-0.28, P < 0.001), and solid tumours as opposed to either leukaemia/lymphomas or non-malignant diseases (OR 0.2, 95% CI 0.07-0.56, P = 0.002) were associated with larger uterine volumes. CONCLUSIONS: Conditioning therapies for SCT, including TBI, had the worst effects on uterine volume and gonadal reserve. Increasing age at treatment and conventional chemotherapy were associated with less detrimental effects on uterine volume.

Polymer-hematite nanocomposites: templating effect of commercial ion-exchangers in the growth of size-controlled iron oxide nanoparticles.

The commercially available ion-exchange resin Amberlite IR120 has been used as the stabilizing agent for the preparation of a size controlled nanostructured hematite phase. The employed synthetic approach, based on the loading of Fe3+ by ion exchange and the subsequent treatment with an aqueous base solution, produces a nanocomposite material with a remarkably high content of oxide nanoparticles (iron content = 18.8% w/w, corresponding to 24.9% w/w of Fe2O3). Scanning electron microscopy and energy dispersive X-ray spectroscopy investigation show that the iron distribution is egg-like and parallels the distribution of the sulfonic groups of the ion-exchanger. Transmission electron microscopy characterization reveals that the size of the ferric oxide nanoparticles in the nanocomposites is narrowly distributed in the 4-6 nm range and that it is the same after the first and the fifth ion-exchange-precipitation cycle. Selected area Electron Diffraction (SAED) analysis of the nanostructured oxide after five ion-exchange-precipitation cycles indicates that it is hematite with a distorted structure.

Posttransplant de novo donor-specific hla antibodies identify pediatric kidney recipients at risk for late antibody-mediated rejection.

The emerging role of humoral immunity in the pathogenesis of chronic allograft damage has prompted research aimed at assessing the role of anti-HLA antibody (Ab) monitoring as a tool to predict allograft outcome. Data on the natural history of allografts in children developing de novo Ab after transplantation are limited. Utilizing sera collected pretransplant, and serially posttransplant, we retrospectively evaluated 82 consecutive primary pediatric kidney recipients, without pretransplant donor-specific antibodies (DSA), for de novo Ab occurrence, and compared results with clinical-pathologic data. At 4.3-year follow up, 19 patients (23%) developed de novo DSA whereas 24 had de novo non-DSA (NDSA, 29%). DSA appeared at a median time of 24 months after transplantation and were mostly directed to HLA-DQ antigens. Among the 82 patients, eight developed late/chronic active C4d+ antibody-mediated rejection (AMR), and four C4d-negative AMR. Late AMR correlated with DSA (p < 0.01), whose development preceded AMR by 1-year median time. Patients with DSA had a median serum creatinine of 1.44 mg/dL at follow up, significantly higher than NDSA and Ab-negative patients (p < 0.005). In our pediatric cohort, DSA identify patients at risk of renal dysfunction, AMR and graft loss; treatment started at Ab emergence might prevent AMR occurrence and/or progression to graft failure.

T-cell therapy for EBV-associated nasopharyngeal carcinoma: preparative lymphodepleting chemotherapy does not improve clinical results.

BACKGROUND: We and others have demonstrated that adoptive cell therapy with Epstein-Barr virus (EBV)-specific autologous cytotoxic T lymphocytes (CTLs) may control disease progression in patients with EBV-associated nasopharyngeal carcinoma (NPC). With the aim of favoring in vivo T-cell expansion, we optimized our cell therapy approach by administering higher doses of EBV-specific CTLs, following lymphodepleting chemotherapy. PATIENTS AND METHODS: Eleven patients with EBV-related NPC in whom conventional treatment failed have been enrolled. Patients received nonmyeloablative lymphodepleting chemotherapy consisting of cyclophosphamide and fludarabine. Two doses of autologous EBV-specific CTLs were subsequently infused, 2 weeks apart. Study end points were feasibility and clinical outcome. RESULTS: All patients enrolled completed the treatment and were assessable for analysis. The median dose of CTLs per infusion was 3.7 × 10(8). Therapy was well tolerated, with no severe adverse events ascribable to either chemotherapy or cell therapy. Disease control (defined as either tumor regression or disease stabilization lasting >4 months) was obtained in 6 of 11 patients, in keeping with previously published results. CONCLUSIONS: Our data confirm that EBV-specific CTL therapy is safe and associated with antitumor activity in patients with advanced NPC. The use of lymphodepleting chemotherapy before high-dose CTL infusion did not enhance the clinical benefit observed in our previous series.

Narrowband ultraviolet B phototherapy in the treatment of cutaneous graft-versus-host disease in oncohaematological paediatric patients.

BACKGROUND: Graft-versus-host disease (GVHD) represents an important complication following allogeneic bone marrow transplantation. In recent years, narrowband ultraviolet B (NB-UVB, 311-313 nm) has been found to be a beneficial adjuvant treatment in patients refractory to first-line immunosuppressive drugs. OBJECTIVES: The aim of this study is to analyse retrospectively the clinical outcome of 10 GVHD paediatric patients treated with NB-UVB therapy. PATIENTS AND METHODS: Ten paediatric patients (six girls and four boys: median age 12.5 years, range 4-20) with cutaneous GVHD were enrolled in the study: five patients with chronic GVHD and five patients with an overlap syndrome GVHD. All patients had already been shown to be resistant to first-choice immunosuppressive protocols, and were treated with NB-UVB phototherapy until a clinical remission of skin lesions occurred. RESULTS: A complete response (absence of lesions) was achieved in 80% of the cases (eight patients) after a median number of 29 treatments, corresponding to a median of 7.5 weeks (52 days) of treatment (range 3-13 weeks), with an average cumulative dose of 28.71 J cm(-2) (range 1.02-70.38 J cm(-2)). Only two patients reported a partial remission (< 18% of body surface area involved). During the follow-up period, a complete remission after 1 year was observed in 75% of patients and after 2 years in 71% of the evaluable patients. CONCLUSIONS: This study provides evidence that NB-UVB phototherapy represents a valid second-line treatment in paediatric patients affected by GVHD and refractory to immunosuppressive first-line treatment.

Isomorphic cutaneous graft-versus-host disease reaction after ultraviolet exposure: clinical, histological and direct immunofluorescence studies of four allo-transplanted patients.

BACKGROUND: Acute and chronic graft-versus-host disease (GVHD) continues to be a major limitation to successful haematopoietic stem cell transplantation. If experimental studies and clinical observations could partially elucidate the pathophysiology of acute GVHD, the biology of chronic GVHD is still much less well understood. OBJECTIVES: The aim of this study is to describe a peculiar photoinduced rash which triggered acute and then chronic lesions of GVHD in four allogenic haematopoietic-transplanted patients and discuss the possible aetiology and treatment. PATIENTS/METHODS: Four patients, two children and two adults affected by either mild or severe chronic GVHD, developed an erythematous rash on sun- or narrow-band ultraviolet B-exposed area, which triggered the onset of acute lesions of GVHD. Any of the patients presented neither a history of photosensitivity nor circulating autoantibodies nor urinary/fecal porphyrine. RESULTS: The histopathologic findings were characterized by an interface dermatitis with sparse perivascular infiltrate of lymphocytes and scattered necrotic keratinocytes, especially in the upper part of epidermis. Direct immunofluorescence studies excluded lupus-like pattern, revealing nests of fluorescent bodies at the dermal-epidermal junction and in papillary dermis. CONCLUSIONS: This peculiar isomorphic reaction of cutaneous GVHD after sun or narrow-band ultraviolet B exposures is described, and the possible mechanism involved is discussed. It may represent an interesting model of progression of chronic GVHD, starting with an acute stage and ending up with chronic clinical and histological findings, especially considering that there is no animal model that fully replicates all of the features of chronic GVHD in humans.

A prospective study on children with initial diagnosis of transient hypogammaglobulinemia of infancy: results from the Italian Primary Immunodeficiency Network.

Transient hypogammaglobulinemia of infancy (THI) is a heterogeneous disorder characterized by reduced serum IgG levels in early infancy. A putative diagnosis is initially made after exclusion of other causes of hypogammaglobulinemia while a definitive diagnosis of THI can only be made a posteriori in patients with normalization of IgG levels. The aim of this study is to characterize clinical and immunological features of children with an initial diagnosis of THI in correlation to natural outcome, and to assess predictive laboratory parameters of clinical evolution for this disorder. We prospectively analysed clinical and immunological characteristics of 77 THI children at initial diagnosis and of 57 patients at follow-up. Memory B cell subsets and in vitro immunoglobulin production were evaluated. Seventy patients (91 percent) showed clinical symptoms. Patients suffered from infections (91 percent), allergies (47 percent) and autoimmune disease (4 percent). During follow-up 41/57 children (72 percent) normalized IgG values, mostly within 24 months of age (p less than 0.001), allowing the diagnosis of THI. The 16 children who did not normalize their IgG levels showed a higher frequency of severe infections and autoimmune disease (p less than 0.01). Moreover, they expressed a reduced frequency of IgM and switched memory B cells (p less than 0.01) and an inability to produce IgG in vitro (p less than 0.02). We conclude that most patients with an initial diagnosis of THI spontaneously recover within 24 months of age and have a benign clinical course, while a subgroup of children with undefined hypogammaglobulinemia share a clinical and immunological profile with other primary immunodeficiencies. Early recognition of children with hypogammaglobulinemia during infancy who are likely to suffer from permanent immunodeficiencies later in life would allow prompt and appropriate laboratory and clinical interventions.

Rehabilitation of chronic graft versus host disease in children. A clinical series.

The study was aimed at evaluating clinical and functional assessment and results obtained following rehabilitative treatment in children affected by chronic graft versus host disease (cGVHD) after allogeneic transplantation of hemopoietic stem cells (HSCT). From 1999 to 2003 we evaluated 6 children with cGVHD after HSCT presenting severe complications and disabilities. Clinical and functional assessment was performed prior to rehabilitative treatment (T1), at follow-up at 6 (T6) and 12 (T12) months after treatment. Each child received a personalized rehabilitative treatment program based on the use of neuromotor re-education techniques, massotherapy, chest rehabilitation and occupational therapy. Six children presented sclerodermoid skin lesions, joint contractures, anchylosis, respiratory insufficiency, postural and walking alterations which led to reduction in motor performance and autonomy in daily living activity. After 1 year of rehabilitation treatment, 3 patients showed improvement in motor performance, 2 remained stable and 1 patient worsened. Rehabilitative treatment associated with pharmacological therapy has proven to be useful in patients affected by cGVHD. We believe that cGVHD is a pathology which must be seen by a physiatrist as early as possible at onset of first cutaneous signs of cGVHD to limit its invalidating evolution.

Development of a portable sensorised handle for the objective assessment of the effectiveness and concordance of intervention plans in dementia.

Dementia is a global issue which is rising rapidly, with 46.8 million people worldwide living with dementia in 2015. This number is expected to increase to 74.7 million by 2030. Some researches show that some kinds of exercises, such as resistance band exercises, would help to improve the memory and other abilities in patients with dementia. However, the true effectiveness of these activities is not really known due to the lack of objective assessment of efforts done during the long intervention time. Moreover, there is no way of measuring the actual activities performed by the patient without direct observation. As a consequence, it is impossible to measure the concordance between the patient and the therapist.

Control of Multifunctional Prosthetic Hands by Processing the Electromyographic Signal.

The human hand is a complex system, with a large number of degrees of freedom (DoFs), sensors embedded in its structure, actuators and tendons, and a complex hierarchical control. Despite this complexity, the efforts required to the user to carry out the different movements is quite small (albeit after an appropriate and lengthy training). On the contrary, prosthetic hands are just a pale replication of the natural hand, with significantly reduced grasping capabilities and no sensory information delivered back to the user. Several attempts have been carried out to develop multifunctional prosthetic devices controlled by electromyographic (EMG) signals (myoelectric hands), harness (kinematic hands), dimensional changes in residual muscles, and so forth, but none of these methods permits the "natural" control of more than two DoFs. This article presents a review of the traditional methods used to control artificial hands by means of EMG signal, in both the clinical and research contexts, and introduces what could be the future developments in the control strategy of these devices.

Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000-2010.

Allogeneic hemopoietic stem cell transplantation (HSCT) is the only method currently available to cure transfusion-dependent thalassemia major that has been widely used worldwide. To verify transplantation distribution, demography, activity, policies and outcomes inside the European Group for Blood and Marrow Transplantation (EBMT), we performed a retrospective non-interventional study, extracting data from the EBMT hemoglobinopathy prospective registry database. We included 1493 consecutive patients with thalassemia major transplanted between 1 January 2000 and 31 December 2010. In total, 1359 (91%) transplants were performed on patients <18 years old, 1061 were from a human leukocyte Ag-identical sibling donor. After a median observation time of 2 years, the 2-year overall survival (OS) and event-free survival (EFS; that is, thalassemia-free survival) were 88 ± 1% and 81 ± 1%, respectively. Transplantation from a human leukocyte Ag-identical sibling offered the best results, with OS and EFS of 91 ± 1% and 83 ± 1%, respectively. No significant differences in survival were reported between countries. The threshold age for optimal transplant outcomes was around 14 years, with an OS of 90-96% and an EFS of 83-93% when transplants were performed before this age. Allogeneic HSCT for thalassemia is a curative approach that is employed internationally and produces excellent results.

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.

Total-body irradiation and melphalan is a safe and effective conditioning regimen for autologous bone marrow transplantation in children with acute myeloid leukemia in first remission. The Italian Association for Pediatric Hematology and Oncology-Bone Marrow Transplantation Group.

PURPOSE: To evaluate the safety and efficacy of a preparative regimen consisting of fractionated total-body radiation (9.9 to 12 Gy) and melphalan (140 mg/m(2) in a single dose) in children with acute myeloid leukemia in first complete remission (CR) given autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Fifty-three children (30 males and 23 females; age range, 1.5 to 18 years) were enrolled onto the study. The median time from first CR to ABMT was 3.5 months (range, 1.4 to 13 months), with 45 patients (85%) undergoing transplantation within 6 months from the diagnosis. Forty-five patients received in vitro marrow purging with standard-dose mafosfamide (100 microg/mL), seven patients were treated with interleukin-2 before marrow collection, and in the remaining child, the marrow was unmanipulated. The median infused cell dose was 1.8 x 10(8)/kg (range, 0.4 to 5.8 x 10(8)/kg). RESULTS: All patients but one achieved hematopoietic engraftment, with a median time to neutrophil recovery of 24 days (range,11 to 66 days). Treatment-related toxicity was moderate and consisted mainly of mucositis. One patient died from cytomegalovirus interstitial pneumonia, and one died from pulmonary hemorrhage. Fourteen patients (26%) relapsed at a median time of 6 months after ABMT (range, 2 to 17 months), with a cumulative relapse probability of 29% (95% confidence interval, 16% to 42%). The 5-year Kaplan-Meier estimate of survival for all 53 patients was 78% (range, 65% to 90%), whereas the overall 5-year disease-free survival was 68% (range, 55% to 81%), with a median follow-up duration of 40 months (range, 7 to 130 months). CONCLUSIONS: These data suggest that, in our cohort of patients, the combination of total-body irradiation and melphalan is safe and associated with good antileukemia activity, making ABMT an appealing alternative for postremission therapy in children with acute myeloid leukemia in first CR.

Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood.

PURPOSE: To evaluate the role of allogeneic bone marrow transplantation (BMT) in children with chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS: Forty-three children with CMML given BMT and reported to the European Working Group on Myelodysplastic Syndrome in Childhood (EWOG-MDS) data base were evaluated. In 25 cases, the donor was a human leukocyte antigen (HLA)-identical or a one-antigen-disparate relative, in four cases a mismatched family donor, and in 14 a matched unrelated donor (MUD). Conditioning regimens consisted of total-body irradiation (TBI) and chemotherapy in 22 patients, whereas busulfan (Bu) with other cytotoxic drugs was used in the remaining patients. RESULTS: Six of 43 patients (14%), five of whom received transplants from alternative donors, failed to engraft. There was a significant difference in the incidences of chronic graft-versus-host disease (GVHD) between children transplanted from compatible/one-antigen-mismatched relatives and from alternative donors (23% and 87%, respectively; P < .005). Probabilities of transplant-related mortality for children given BMT from HLA-identical/one-antigen-disparate relatives or from MUD/ mismatched relatives were 9% and 46%, respectively. The probability of relapse for the entire group was 58%, whereas the 5-year event-free survival (EFS) rate was 31%. The EFS rate for children given BMT from an HLA-identical sibling or one-antigen-disparate relative was 38%. In this latter group, patients who received Bu had a better EFS compared with those given TBI (62% v 11%, P < .01). CONCLUSION: Children with CMML and an HLA-compatible relative should be transplanted as early as possible. Improvement of donor selection, GVHD prophylaxis, and supportive care are needed to ameliorate results of BMT from alternative donors.