Growth and development following marrow transplantation for leukemia

One hundred forty-two patients between the ages of 1 and 17 years who survived disease-free more than 1 year after marrow transplantation for hematologic malignancy had growth and development evaluations from one to 14 years posttransplant (median 4 years). Prior to transplant all children received multiagent chemotherapy and 55 also received central nervous system irradiation, but none had growth and development evaluations. Marrow transplant preparation included high-dose chemotherapy and total body irradiation (TBI) given as a single dose of 9.2 to 10.0 Gy (79 patients) or as fractionated doses of 2.0 to 2.25 Gy/d for six to seven days (63 patients). After transplant abnormal thyroid function was present in 39%. Stimulated 11-desoxycortisol levels were subnormal in 24% of patients evaluated. Growth hormone (GH) deficiency was present in 17 of 25 children who received previous cranial irradiation. Partial GH deficiency was present in 4 of 25 who received previous cranial irradiation and in 6 of 18 who had not received cranial irradiation. Height velocity was decreased in all patients. After transplant, height was significantly influenced by chronic graft-v-host disease and single-dose TBI. Sixty-eight percent had delayed development of secondary sexual characteristics. Gonadal failure occurred in nearly all who were postpubertal at transplant. While it is not possible to determine how many of these endocrine abnormalities occurred as a result of treatment administered prior to transplantation, these data do demonstrate that children who become long-term survivors after marrow transplantation for hematologic malignancy have endocrine abnormalities that adversely affect growth and development.     

Value of chest radiography in excluding traumatic aortic rupture

A retrospective review of chest radiographs from 205 patients with blunt chest trauma who also underwent aortography was performed. Forty-one of the 205 had aortographically proved aortic rupture. Discriminant analysis of 16 radiographic signs indicated that the most discriminating signs were loss of the aorticopulmonary window, abnormality of the aortic arch, rightward tracheal shift, and widening of the left paraspinal line without associated fracture. No single or combination of radiographic signs demonstrated sufficient sensitivity to indicate all cases of traumatic aortic rupture on plain chest radiographs without the performance of a large number of aortographically negative studies. The bedside anteroposterior "erect" view of the chest proved far more valuable than the supine view in detecting true-negative studies. Despite significant reader variability in the interpretation of the various radiographic signs, in general the analysis confirmed the role of chest radiography in this clinical situation, but suggests that its most beneficial use is in excluding the diagnosis and eliminating unwarranted aortography rather than in predicting aortic rupture.     

Long-term follow-up of gastric histology after Helicobacter pylori eradication

Helicobacter pylori causes chronic active gastritis and is thought to be associated with the development of gastric atrophy, intestinal metaplasia and carcinoma. As the effect of H. pylori eradication on this process is poorly understood, we sought to determine the long-term effects of H. pylori eradication on gastric histology. Fifty-four patients with duodenal ulceration associated with H. pylori infection received H. pylori eradication therapy in 1985/86 and either remained infected (n= 22) or had the infection eradicated (n= 32); patients were followed up by endoscopy with gastric antral biopsy for 7.1 years (mean). Histopathological analysis of gastric antral mucosa from patients rendered H. pylori-negative revealed a marked decrease in both inflammatory cells within the lamina propria and intraepithelial neutrophils and an increase in epithelial mucinogenesis. Gland atrophy remained unchanged in both H. pylori-positive and -negative patients. When examined for the presence and severity of intestinal metaplasia, there was neither a difference between the two patient groups nor a change with time. These data demonstrate that significant long-term improvements in gastric histology accompany H. pylori eradication when compared with histology in patients with persistent infection. Whether this confers a protective effect by reducing the risk of gastric carcinoma remains unknown.     

Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease

To reduce the morbidity and mortality associated with unrelated donor bone marrow (BM) transplantation and potentially extend the pool of suitable donors, cryopreserved unrelated donor umbilical cord blood was considered as an alternate source of hematopoietic stem cells for transplantation. Patients with leukemia, BM failure syndrome, or inborn error of metabolism were eligible for a phase I clinical trial designed to estimate the risk of graft failure and severe acute graft-versus- host disease after transplantation of umbilical cord blood from unrelated donors. As of December 21, 1995, unrelated donor umbilical cord blood was used to reconstitute hematopoiesis in eighteen patients aged 0.1 to 21.3 years weighing 3.3 to 78.8 kg with acquired or congenital lympho-hematopoietic disorders or metabolic disease. Patients received either HLA-matched (n = 7) or HLA-1 to 3 antigen disparate (n = 11) grafts collected and evaluated by the New York Blood Center (New York, NY). The probability of engraftment after unrelated donor umbilical cord blood transplantation was 100% with no patient having late graft failure to date. The probability of grade III-IV acute graft-versus-host disease at 100 days was 11%. With a median follow-up of 6 months (range, 1.6 to 17 months); the probability of survival at 6 months is 65% in this high risk patient population. We conclude that cryopreserved umbilical cord blood from HLA-matched and mismatched unrelated donors is a sufficient source of transplantable hematopoietic stem cells with high probability of donor derived engraftment and low risk of refractory severe acute graft-versus-host disease. Limitations with regard to recipient size and degree of donor HLA disparity remain to be determined.     

Role of sensory afferent neurons in hypertonic damage and restitution of the rat gastric mucosa

BACKGROUND & AIMS: Gastric mucosal hyperemia is a protective response mediated at least in part by the response of sensory afferent neurons to hydrogen ions. The aim of this study was to determine if other pathways to the hyperemic response are present and if these neurons have an effect exclusive of hyperemia on mucosal protection and repair. METHODS: Rat sensory afferent neurons were ablated by capsaicin treatment. Chambered stomachs were damaged by hypertonic saline followed by either acidic or neutral isotonic saline. Blood flow was measured by laser Doppler velocimetry, and mucosal morphology was quantitatively evaluated by microscopy. RESULTS: Mucosal damage alone evoked a strong hyperemic response in both control and ablated rats. Ablated rats lost gastric protection despite this hyperemic response. Acid exposure after damage sustained the hyperemic response. Rapid epithelial restitution occurred faster (even over hemorrhagic lesions) in control rats. CONCLUSIONS: The hyperemic response to mucosal damage alone is not mediated by sensory neurons. Protection of the stomach by sensory afferent neurons occurs by mechanisms also unrelated to their elicitation of hyperemia. Restitution during acid challenge is enhanced by the sustained hyperemic response mediated through sensory afferent neurons. (Gastroenterology 1996 Dec;111(6):1474-83)     

Lymphocyte depletion of donor bone marrow by counterflow centrifugal elutriation: results of a phase I clinical trial

We report here the results of a phase I clinical trial using counterflow centrifugal elutriation (CCE) for the removal of donor T lymphocytes before allogeneic bone marrow transplantation (BMT). Thirty- eight patients received lymphocyte-depleted allografts from HLA- identical, MLR-nonreactive sibling donors. The patients entered onto the study were either at high risk on the basis of age (median, 39 years) or disease status (acute leukemia in early relapse [ER], chronic myelogenous leukemia [CML] in accelerated phase [AP], or therapy resistant [RES] lymphoma). All patients received a standard lymphocyte dose of 1 x 10(6) morphologic lymphocytes per kilogram ideal body weight (BW) and were maintained on cyclosporine A (CsA) for 170 days after BMT. Prompt engraftment occurred in 37 of 38 patients with a median time to absolute neutrophil count (ANC) greater than 500/microL of 18 days. Although acute graft-v-host disease (GVHD; clinical stage I or greater) was observed in 45%, it was limited to the skin in all but five patients. Survival was related to disease status at the time of BMT. Among patients with acute leukemia in first or second remission, CML in chronic phase (CP) or lymphoma in partial remission (PR), 64% are currently alive, in contrast to 31% of patients with acute leukemia in third remission or early relapse, CML in second CP or AP, or RES lymphoma. Median follow-up for all patients was 351 days (range, 105 to 711 days). We conclude that this procedure is safe and warrants further evaluation in a randomized efficacy trial.