Immunity to Polioviruses and Tetanus After Bone Marrow Transplantation in Children

Immunity to tetanus toxoid and polioviruses was studied in 34 (27 allografted, 7 autografted) children who underwent bone marrow transplantation (BMT). At a median time of 3 years after BMT, only one recipient was seronegative for tetanus toxoid. On the contrary 73 % of children were seronegative for at least one of the three poliovirus types and 30% for all vim types. Undetectable antibody titers were more frequently found against type 3 than the other two types. We recommend that reimmunizations of children after BMT be based on serologic tests for antibody titers.     

Immunity to Polioviruses and Tetanus After Bone Marrow Transplantation in Children

Immunity to tetanus toxoid and polioviruses was studied in 34 (27 allografted, 7 autografted) children who underwent bone marrow transplantation (BMT). At a median time of 3 years after BMT, only one recipient was seronegative for tetanus toxoid. On the contrary 73 % of children were seronegative for at least one of the three poliovirus types and 30% for all vim types. Undetectable antibody titers were more frequently found against type 3 than the other two types. We recommend that reimmunizations of children after BMT be based on serologic tests for antibody titers.     

Second Bone Marrow Transplantation in Eight Children

Between 1985 and 1989, eight children underwent two successive bone marrow transplantations. The initial disease was chronic myelomonocytic leukemia in three patients, chronic myelocytic leukemia in two, acute M7 nonlymphoblastic leukemia in one, sickle cell anemia in one, and thalassemia major in one. The preparation in view of the second grafting included high-dose chemotherapy in all patients, associated with antithymocytic globulin transfusion and total nodal irradiation in three patients. Hematological recovery was similar after both graftings. Infectious complications were not more common following the second graft than after the first one. On the other hand, the rates of rejection and graft-versus-host disease were lower, probably due to a more intensive immunosuppressive therapy. The prognosis of chronic leukemia relapsing after a first graft does not seem to be improved by a second attempt.     

Comparison of Autologous and Allogeneic Bone Marrow Transplantation in Children with Acute Leukemia

Thirty-one patients with acute non-lymphocytic leukemia (18 patients) or with high-risk refractory acute lymphocytic leukemia (13 patients) underwent bone marrow transplantation between March 1980 and March 1990. The high-dose conditioning regimen employed included cyclophosphamide followed by fractionated total body irradiation (12 GY). Fourteen patients who had an HLA-identical sibling donor received allogeneic bone marrow transplantation (ailo-BMT); the other 17 patients received autologous bone marrow transplantation (auto-BMT) purged with 4-hydroperoxycyclophosphamide (4HC). Four of the 14 allo-graft recipients died of leukemic relapse and 2 others died of graft-versus-host disease. Three of the 17 auto-graft recipients died of relapse and 1 suffered relapse in the testes. The actuarial risk of relapse was 29% for the allo-BMT patients and 24% for the auto-BMT patients (P<0.05). The event-free survival rate at five years was 57% and 74% respectively (P<0.05). Although there was no difference between them, a trend toward a higher survival rate and a lower mortality and morbidity was observed in the auto-BMT group. These results suggest that autologous bone marrow transplantation purged with 4HC is an effective and useful treatment for children with acute non-lymphocytic and lymphocytic leukemia who have no HLA-identical donor.     

Isolated Intraspinal Relapse Of Neuroblastoma After Autolocous Bone Marrow Transplantation

Neuroblastoma may present with spinal cord compression due lo dumbbell extension of thoracic or abdominal disease. Isolated intraspinal involvement as the sole sate of relapse is rare. Two infants with poor-prognosis stage IV neuroblastoma presented early after high-dose therapy and autologow bone marrow transplant with isolated spinal relapse heralded by misleading symptom. The rarity of such isolated relapses is reviewed, and an etiologic hypothesis is proposed.     

Isolated Intraspinal Relapse Of Neuroblastoma After Autolocous Bone Marrow Transplantation

Neuroblastoma may present with spinal cord compression due lo dumbbell extension of thoracic or abdominal disease. Isolated intraspinal involvement as the sole sate of relapse is rare. Two infants with poor-prognosis stage IV neuroblastoma presented early after high-dose therapy and autologow bone marrow transplant with isolated spinal relapse heralded by misleading symptom. The rarity of such isolated relapses is reviewed, and an etiologic hypothesis is proposed.     

Evaluating the Patients with Thalassemia Major for Long-Term Endocrinological Complications After Bone Marrow Transplantation

The aim of this study was to evaluate the endocrinological complications of the patients with thalassemia major (TM) who underwent bone marrow transplantation (BMT) and followed-up more than two years in our center, prospectively. “BMT group” consisted of 41 patients with TM. The mean age was 12.4 ± 5.4 years and transplantation age was mean 7.5 ± 4.9 years. Post-BMT follow-up lasted from 24 to 122 months (mean 65.07 months). Also, 32 TM patients with similar age group and same history of transfusion and chelation therapy were recruited for the study as “control (C) group”. The weight SDS score after transplantation was found better than before transplantation (p = 0.010). There was a negative correlation between height SDS and BMT age (p = 0.008). The height SDS scores were better in patients whose BMT age was under seven years old compared to those older than seven years old (p = 0.02). Z-scores of femur neck and L_2-4 vertebrae DEXA were decreased (p = 0.032, p = 0.0001) and incidence of insulin resistance increased (p = 0.01) in patients with increased BMT age. The risk of gonadal insufficiency was significantly lower in the patients who underwent BMT <7 years of age (p = 0.009). There was no statistically significant relationship between BMT age and complications such as hypothyroidism, hypoparathyroidism, and adrenal insufficiency. The patients with TM should be evaluated for transplantation in early stage of the disease, especially before the age of seven years. Because the BMT cannot correct the endocrinological complications of TM completely, the patients should be followed up regularly after the transplantation.     

Sensory-Motor and Cognitive Functioning in Children Who Have Undergone Bone Marrow Transplantation

ABSTRACT. Sensory-motor and cognitive functioning was investigated in a group of 32 children treated with bone marrow transplantation (BMT), 1–6 years after treatment. Twenty-five of the patients had suffered from leukemia. The BMT procedure had involved a regimen of cytostatic drugs and, for leukemia patients, total body irradiation at a dose of 10 Gy, administered in one session. Cytostatic drugs and irradiation are known to be potentially neurotoxic, particularly when combined. The examination involved four neuropsychological tests of sensory-motor and cognitive functioning, as well as an age-appropriate intelligence test. For control the bone marrow donors (n=32), siblings of the patients, were also investigated. A pronounced delay in motor development was found in four children, who had been treated with BMT including total body irradiation before 3 years of age. Patients between 3 and 11 years of age at BMT were at a slight disadvantage, compared to donors, on tasks involving perceptual and fine motor speed. In older patients no deficits were observed.     

Autologous Bone Marrow Transplantation in Pediatric Solid Tumors

During the last 5 years massive chemotherapy and autologous bone marrow transplantation have been increasingly explored in the treatment of pediatric solid tumors, mainly for neuroblastoma, Ewing's sarcoma, rhabdomyosarcoma, Wilms' tumor, germ cell tumors, osteosarcoma, and retinoblastoma. Although the disease course could be changed successfully in most instances, the long-term survival has not yet been improved much over the best available conventional treatments. Despite this, in responding relapsed patients this approach seems promising and may represent the only chance of cure. New and better induction regimens are needed.     

Antiinfective Prophylaxis with Ceftazidime and Teicoplanin in Children Undergoing High-Dose Chemotherapy and Bone Marrow Transplantation

Sixty children treated for solid tumors with high-dose chemotherapy followed by bone marrow transplantation were randomly assigned to one of two antibiotic protocols. Group A received prophylaxis consisting of ceftazidime plus teicoplanin beginning before the onset of aplasia and fiver; group B received exactly the same antibiotic regimen but beginning at the onset of fever. The two groups were compared in terns of the rate of septicemia, fever of unknown origin, the time-lapse before the appearance of septicemia, the sensitivity of the causative organisms to the antibiotics, the effect of the latter on the intestinal flora, and the rate of fungal infections. The incidence of septicemia was significantly lower in group A (6.6%) than in group B (24.0%), mainly due to the prevention of episodes of early onset. Similarly, the appearance of the first episode of fever was delayed in group A, and the overall duration was reduced. Amphotericin B was prescribed empirically with the same rule in both groups, but three children in group A did not require amphotericin B. The effect on the intestinal flora was similar in the two groups; it must, however, be closely monitored so that the presence of potential pathogens can be dealt with appropriately.     

Report on the International Workshop of the Kind Philipp Foundation on Late Effects After Bone Marrow Transplantation in Childhood Malignancies

This report is a short summary of an international workshop on late effects after bone marrow transplantation in pediatric patients. Main topics of the report are chronic GVHD and immune reconstitution and the late effects of this kind of treatment on growth, respiratory function, the endocrinological system, teeth, and eyes. The development of secondary tumors is discussed as well as the influences on the central nervous system and behavior of children.     

Incubation Of Autolocous Bone Marrow Graft with Asta Z 7557: Comparative Studies of Hematological Reconstitution After Purged or Nonpurged Bone Marrow Transplantation

Thirty-three patients with advanced solid tumors were treated by high-dose chemotherapy (combined high-dose melphalan), followed by cryopreserved autologous bone marrow transplantation (ABMT). Thirteen of them had bone marrow (BM) tumor involvement at diagnosis, and BM harvest was purged with 50 μglml ASTA Z 7557 before cryopreservation. Following incubation, in vitro growth of granulomonocytic colony-forming cells (GM-CFC) was regularly inhibited (>99%). Hemopoietic reconstitution after purged and nonpurged ABMT was studied. All patients experienced engraftment. However, peripheral leukocyte and granulocyte recoveries were delayed significantly in patients receiving purged BM (mean 27 and 26 days) compared with those observed in patients receiving nonpurged BM (mean 18 and 18 days). These results confirm that purged BM, despite GM-CFC depletion after in vitro treatment, ensures engraftment after high-dose chemotherapy, but prolonged pancytopenia is observed and postgraft hemopoietic recovery is delayed. A clinical trial is necessary to evaluate the efficiency of the purging technique in eradicating residual tumor cells.     

Interleukin 2 Immunotherapy in Children with Neuroblastoma after High-Dose Chemotherapy and Autologous Bone Marrow Transplantation

Four children with persistent neuroblastoma after marrow ablative chemoradiotherapy and autologous bone marrow transplantation received continuous infusion of recombinant interleukin 2, 75 to 120 days after the graft. Recombinant interleukin 2 therapy did not induce any major or nonreversible toxicity, hematological toxicity in particular. One patient entered complete remission for 9 months and a second patient had a long-lasting normalization of urinary catecholamine metabolites with more than 50% regression of bone marrow metastases (8 months). In three children, recombinant interleukin 2 and a second patient entered complete remission for 9 months therapy was followed by major increase and activation of circulating natural killer cells which amounted to 80% of the circulating mononuclear cells.     

Listeria Septicemia Complicating Bone Marrow Transplantation for Diamond-Blackfan Syndrome

Infection with Listeria monocytogenes is uncommon in patients receiving cytotoxic chemotherapy, and is even rarer among recipients of bone marrow transplantation. Hemosiderosis, either idiopathic or caused by transfusion, appears to be another risk factor. We report a 3-year-old Chinese girl with transfusion-dependent Diamond-Blackfan syndrome who had L. monocytogenes septicemia when she received an allogeneic bone marrow transplantation. She was treated successfully with intravenous ampicillin. Our case adds to the clinical evidence that patients with iron overload are susceptible to listeriosis, particularly when they are immunocompromised and do not receive iron-chelation treatment.     

Listeria Septicemia Complicating Bone Marrow Transplantation for Diamond-Blackfan Syndrome

Infection with Listeria monocytogenes is uncommon in patients receiving cytotoxic chemotherapy, and is even rarer among recipients of bone marrow transplantation. Hemosiderosis, either idiopathic or caused by transfusion, appears to be another risk factor. We report a 3-year-old Chinese girl with transfusion-dependent Diamond-Blackfan syndrome who had L. monocytogenes septicemia when she received an allogeneic bone marrow transplantation. She was treated successfully with intravenous ampicillin. Our case adds to the clinical evidence that patients with iron overload are susceptible to listeriosis, particularly when they are immunocompromised and do not receive iron-chelation treatment.     

Lymphocytes after Autologous and Allogenic Bone Marrow Transplantation

Lymphocyte reconstitution after bone marrow transplantation (BMT) was analyzed using two-color flowcytometry in 18 patients and the differences between allogenic and autologous BMT were studied. The CD8 (+) CDllb (+) and CD8 (+) Leu7 (+) suppressor sub sets were increased while the CD4 (+) 2H4 (+) suppressor inducer subset was decreased in both groups after BMT. These variations of suppressor associated subsets persisted for more than 100 days and were considered to be related to immunologic abnormalities in post-BMT patients. In addition, Ia (+) T cells were increased in both autologous and allogenic BMT patients. Thii increase appears not to be caused by reaction to allo-antigens, but rather reflects the reconstitution of the lymphocyte system after BMT. In contrast, the CD16 (t) NK cell subset was increased specifically in allogenic BMT patients and only for a short time following transplantation.     

Early Toxicity of Intensified Conditioning with Etoposide Combined with total Body Irradiation/Cyclophosphamide or Busulfan/Cyclophosphamide in Children Undergoing Autologous or Allogeneic Bone Marrow Transplantation

In recent years, high dose chemotherapy followed by bone marrow rescue has been established as a common treatment of hematologic and solid tumor malignancies. Despite unequivocal success, relapse after transplant remains a serious problem, being the main cause of treatment failure. In an attempt to reduce relapse rates, we intensified the conditioning regimens consisting of busulfan/cyclophosphamide versus fractionated total body irradiation (f-TBI)/ cyclophosphamide by the addition of high dose eloposide. Toxicity profiles of 25 pediatric patients with hematologic malignancies undergoing intensified conditioning did not differ significantly between the two groups, except for a higher incidence of veno-occlusive disease in busulfan-treated patients (3 of 13 patients) compared with the TBI group (0 of 12 patients). We observed no transplant-related mortality in neither group. Regimen-associated morbidity was moderate and reversible in all cases. Five patients died in each treatment arm, due to relapse of the underlying disease. We conclude that both regimens are feasible in marrow transplantation of pediatric patients. Open randomized trials are needed to assess the efficacy of intensified conditioning in terms of disease-free survival.     

Allogeneic Bone Marrow Transplantation in Childhood Leukemia

Allogeneic bone marrow transplantation was performed in 94 patients with hematologic malignancies or other various diseases during the period between March 1982 and November 1990 at Tokai University Hospital. Projected disease-free survival rates of HLA genotypically identical marrow recipients were 88.9% for chronic myeloid leukemia transplanted in the first chronic phase (N = 9), 90.9% for acute leukemia in the first complete remission (N = 15), 54.5% for acute leukemia in later remissions (N = 14), 62.5% for solid tumors (N = 8) and 0% for patients transplanted in relapse (N = 7). The rate for HI A-mismatched marrow recipients with leukemia was 27.8% (N = 16). For patients with non-neoplastic diseases it was 100% regardless of HLA-compatibility (N = 26). The quality of life in long-term surviving pediatric marrow recipients has been acceptable. Common abnormalities among survivors are long-lasting hypogonadism due to radiation and subclinical impairment of lung function in the first year post-BMT. About two-thirds of children experienced a transient decrease in growth velocity in the immediate posttransplant period.