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Biomedical subjects

H M Shulman

Publications and source records attributed to H M Shulman.

At least 73 records · Page 4Linked to original sources
PubMed1984

Allogeneic marrow transplantation in the treatment of preleukemia.

Ten patients with preleukemia and life-threatening pancytopenia were treated with marrow transplantation. In all ten cases allogeneic marrow was successfully engrafted. In three patients prepared for transplantation with cyclophosphamide alone, the abnormal cell clone either persisted or reemerged within 6 months of transplantation. The other seven patients were treated with cyclophosphamide plus total body irradiation before transplantation and six of the seven are alive and well without evidence of disease from 7 to 25 months after transplantation. These results suggest that cyclophosphamide alone before marrow transplantation is incapable of eradicating the abnormal clone. Cyclophosphamide combined with total body irradiation appears more effective, although more time is needed for full evaluation of results. This experience also emphasizes the importance of performing chromosome studies before transplantation for pancytopenic states in order to identify cases of preleukemia.

Adolescent↗
PubMed1984

Fatal Epstein-Barr-virus-associated proliferation of donor B cells after treatment of acute graft-versus-host disease with a murine anti-T-cell antibody.

Two patients with acute leukemia were treated with chemoradiotherapy and allogeneic bone marrow transplantation. Despite the prophylactic use of methotrexate after grafting, both patients developed severe graft-versus-host disease that was refractory to treatment with methylprednisolone. The graft-versus-host disease was then treated with a monoclonal antibody, 64.1, that reacts with a p19 antigen on human T cells. The disease responded dramatically to this treatment, but both patients subsequently developed a fatal polyclonal lymphoproliferative disorder arising in donor-derived B cells. Hybridization studies showed Epstein-Barr virus in both tumors. The combined effect of severe end-stage graft-versus-host disease and potent immunosuppressive therapy probably resulted in a progressive immunodeficiency syndrome that abrogated the T-cell-mediated surveillance mechanism that normally modulates the proliferation of Epstein-Barr-virus-infected B lymphocytes.

Adult↗
PubMed1983

Ocular manifestations of graft-v-host disease.

Graft-v-host disease is the major complication of bone marrow transplantation for the leukemias and aplastic anemia. In the clinical evaluation of eye problems of patients with acute graft-v-host disease, findings reveal a disease process of keratoconjunctivitis that appears to represent a specific pathologic eye syndrome in which the conjunctivae and occasionally the cornea represent an immunologic target of graft-v-host disease. Additional studies of eye problems of chronic graft-v-host disease reveal the persistent nature of keratitis sicca and the morbid sequelae of the immunoincompetent patient.

Acute Disease↗
PubMed1983

The predictive value of elevated labial saliva sodium concentration: its relation to labial gland pathology in bone marrow transplant recipients.

Labial minor gland salivary flow rate and sodium concentration were analyzed in relation to 1) histologic findings in labial biopsy specimens and 2) the occurrence of chronic graft-versus-host disease (GVHD) in patients who received bone marrow transplants. Biopsy specimens and samples were obtained from 61 recipients of marrow transplants (including three twins) 51 to 1,260 days post transplantation. Labial saliva sodium concentrations were elevated in some patients, and these increases were associated with inflammation and destruction of minor salivary gland acini and ducts by chronic GVHD or other factors. The predictive value of the salivary sodium changes in evaluating labial salivary gland pathologic changes was 91 per cent, and the sensitivity was 74 per cent. Thus, if a transplant recipient is found to have an elevated labial saliva sodium level, then the probability that he has pathologic labial gland changes is 91 per cent. When analyses were restricted to include only patients who received no irradiation during transplantation, then elevated labial saliva sodium concentration was significantly associated with the occurrence of chronic GVHD. The sensitivity of this relationship was 42 per cent, but the predictive value was 100 per cent. Thus, if a nonirradiated transplant recipient is found to have an elevated labial saliva sodium concentration, then it is virtually certain that he has chronic GVHD. We found no significant changes in labial saliva flow rates in these bone marrow transplant recipients.

Adolescent↗
PubMed1983

Disordered salivary immunoglobulin secretion and sodium transport in human chronic graft-versus-host disease.

Whole saliva samples and lip biopsies were collected from 12 allogeneic bone marrow transplant recipients who developed extensive chronic graft-versus-host disease (GVHD) and from 10 healthy allogeneic and syngeneic recipients without GVHD. Six of ten biopsies from patients with chronic GVHD had lichenoid stomatitis or sialadenitis, or both, with sialodochitis. Seven of nine biopsies from patients free of chronic GVHD were entirely normal, and two had either mild glandular or mucosal changes. Salivary gland involvement in chronic GVHD was associated with decreased or absent levels of salivary IgA and inorganic phosphate, decreased salivary flow rates, and increased concentrations of salivary sodium, albumin, and IgG. The most striking abnormalities were found in patients with histologic evidence of sialadenitis. In contrast, marrow transplant recipients without chronic GVHD had normal salivary immunoglobulin and electrolyte levels. Secretory IgA deficiency may contribute to the frequent sinobronchial infections observed in patients with chronic GVHD.

Adolescent↗
PubMed1983

Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings.

One hundred ten of 175 patients with aplastic anemia conditioned by cyclophosphamide had sustained engraftment of marrow from human leukocyte antigen (HLA)-identical siblings and lived for more than 6 months. Forty-nine of the 110 patients developed chronic graft-versus-host disease between 85 and 464 days. Ninety-seven patients are alive from 1.4 to 11 years after engraftment; 13 died between 208 and 726 days. Twenty of the 36 surviving patients with chronic graft-versus-host disease have Karnofsky performance scores of 100%, 7 of 90%, 5 of 80%, 1 of 70%, 2 of 60%, and 1 of 40%. Our analysis, using a binary logistic regression model, identified three factors predicting chronic graft-versus-host disease: moderate to severe acute graft-versus-host disease with an estimated relative risk of 11.65; increasing patient age; and the use of viable donor buffy coat cells in addition to the marrow to prevent graft rejection. The last two factors were significant only in patients without acute graft-versus-host disease.

Adolescent↗
PubMed1982

Rapid cytologic diagnosis of cytomegalovirus interstitial pneumonia on touch imprints from open-lung biopsy.

The diagnostic utility of Wright-Giemsa-stained touch imprints for identifying cytomegalovirus (CMV) in open-lung biopsies from marrow transplant recipients was studied. Of 41 consecutive biopsy specimens, 18 had culturally proven CMV, and 15 had typical intranuclear and intracytoplasmic inclusion bodies on permanent histologic sections. Wright-Giemsa-stained touch imprints from ten of the 15 biopsy specimens with CMV had characteristically enlarged cells containing 20-75 round to oval intracytoplasmic inclusions while only rarely containing intranuclear inclusions. The diagnosis of CMV from Wright-Giemsa-staining imprints (10/15) was superior to hematoxylin and eosin (H & E)-stained touch imprints (5/15) and H & E-stained frozen sections (2/15). Two cases of CMV had Papanicolaou-stained imprints that also demonstrated both intranuclear and intracytoplasmic inclusions. This simple technic of examining cytologic imprints from open-lung biopsy specimens will rapidly identify more than 50% of all confirmed cases of CMV, allowing earlier and possibly more successful antiviral therapy.

Biopsy↗
PubMed1982

The fine structure of human rectal epithelium in acute graft-versus-host disease.

We compared the fine structure of the biopsied rectal mucosa of seven allogeneic bone marrow transplant recipients who had gastrointestinal graft-versus-host disease (GVHD) with that of four recipients without GVHD. In GVHD, lymphocytes formed the predominant cellular infiltrate. Lymphocytes indented the cytoplasmic membranes of enterocytes by point contact, extended broad pseudopods to the nuclear membranes of the enterocytes, and surrounded desmosomes. The membranes of target cells were never breached, however. We hypothesize that these lymphocyte-to-epithelial-cell contacts represent the recognition phase of alloimmune T-lymphocyte cytolysis. Damage to the enterocytes resulted in both coagulative necrosis and "apoptosis" (the development of membrane-bound cell fragments--"apoptotic bodies"). Epithelial injury and lymphocytic infiltration predominated in the bases of the crypts in mild GVHD and extended to the surface epithelium in severe GVHD. Chemoradiotherapy-induced injury, present early post-transplant, was diffuse and severe but transient. In GVHD, damage to the enterocytes, necrosis, and intercellular edema extended beyond the time of resolution of chemoradiotherapy-induced injuries. Patients without GVHD, studied after resolution of chemoradiation injury, had rectal epithelium with little or no injury and no evidence of either increased numbers of lymphocytes or of the intimate lymphocyte-to-epithelial-cell contacts described in those with GVHD.

Anemia, Aplastic↗
PubMed1982

Engraftment of DLA-nonidentical unrelated canine marrow after high-dose fractionated total body irradiation.

Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given eigher as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to 4 x 10(8) cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis. In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after i vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.

Animals↗
PubMed1982

Immediate and delayed neurotoxicity after mechlorethamine preparation for bone marrow transplantation.

Twenty-four patients, including two with aplastic anemia and 22 with malignancy, underwent marrow transplantation after preparation with mechlorethamine, 0.3 to 2.0 mg/kg body weight. Fourteen of the 21 neurologically evaluable recipients developed immediate neurotoxicity a median of 4 days after treatment (range, 0 to 34 days). Confusion and disorientation were observed in six patients, headache in six, hallucinations n four, lethargy in four, tremors in three, paraplegia in one, seizure in one, and vertigo in one. Whereas acute symptoms cleared in 11 patients, three remained symptomatic until death. Twelve evaluable patients survived more than 60 days; all six with previous acute toxicity subsequently developed delayed onset of new neurologic findings (personality change, confusion, seizure, diplopia, or dementia) a median of 169 days (range, 70 to 248 days) after treatment. Cerebrospinal fluid analysis was usually normal but cerebral computed tomographic scans showed ventricular enlargement and electroencephalograms showed diffuse slowing. Postmortem histologic examination of brain showed neuronal degenerative changes with increased vascularity, gliosis, and perivascular fibrosis. Neurotoxicity appeared to increase with age and mechlorethamine dose and was commoner in patients given additional procarbazine or cyclophosphamide.

Adolescent↗
PubMed1982

Frozen section diagnosis of cytomegalovirus infections.

We studied the standard frozen section as a diagnostic method for cytomegalovirus infection of the lung in bone marrow transplant recipients. Fifty-nine patients with cytomegalovirus pneumonia diagnosed by open lung biopsy were studied. The sensitivity of frozen section was compared with that of paraffin section, cytology of imprints prepared from the tissue sample, and viral culture. Fifteen percent of the cases were diagnosable at frozen section alone, and 44% by cytology alone. This confirms our previous study and indicates that frozen section unaided by more specific indentification methods provides low sensitivity even in cytomegalovirus-infected cells, which probably show the most easily identified cytopathic effects of any virus. This low sensitivity underscores the need for the additional sensitivity and specificity which may be contributed by immunolabeling techniques to rapid viral diagnosis.

Biopsy↗
PubMed1982

Acute and chronic graft-versus-host disease in dogs given hemopoietic grafts from DLA-nonidentical littermates. Two distinct syndromes.

We recognized two distinct clinical and histologic syndromes of acute and chronic graft-versus-host disease (GVHD) in irradiation chimeric dogs given hemopoietic grafts from DLA-nonidentical littermate donors. Clinically acute GVHD developed, with a median onset of 13 days after the transplant, and was characterized by skin erythema, jaundice, diarrhea, and gram-negative infections; the median survival of these dogs was 29.5 days. Chronic GVHD developed a median of 124 days after the transplant and was characterized by generalized skin ulcerations, massive ascites, and gram-positive infections; the median survival of these dogs was 150 days. Chronic GVHD could be distinguished histologically from acute GVHD by epidermal atrophy and dermal fibrosis and by bile duct proliferation, bridging, piecemeal necrosis, and portal fibrosis in the liver. Questions related to GVHD in man can be investigated in this model of acute and chronic GVHD in a large outbred species.

Acute Disease↗
PubMed1981

Bone marrow transplantation for acute myelosclerosis.

Four patients with acute myelosclerosis were treated with chemoradiotherapy and bone marrow transplantation. Three of the four had prompt engraftment with greater than 0.10 X 10(9) granulocytes/liter three weeks after transplantation. One patient continues in complete remission one year after transplantation. One patient experienced a partial remission and two patients died early in the post-transplantation period. Marrow fibrosis disappeared in three of the four patients. The patient with residual marrow fibrosis died 22 days after transplantation. It is apparent that marrow fibrosis is reversible. In view of the absence of other effective therapy, intensive therapy with marrow transplantation should be considered as primary therapy for patients with acute myelosclerosis who have a suitable marrow donor.

Acute Disease↗
PubMed1981

Gastrointestinal radiographic features of human graft-vs.-host disease.

Following allogeneic bone marrow transplantation, graft-versus-host disease (GVHD) develops when the foreign donor lymphoid graft mounts an immunologic reaction against the skin, liver, and gastrointestinal tract of the host. The GVHD syndrome is characterized by skin rash, hepatocellular dysfunction, and secretory diarrhea with destruction of intestinal mucosa. The gastrointestinal radiographic manifestations of proven GVHD were studied in 16 allogeneic marrow recipients transplanted for aplasia (nine) or leukemia (seven). The radiographic findings revealed three distinct phases that correlated with the duration of active gastrointestinal GVHD: (1) Acute phase-seven examinations were performed 4-15 days after the onset of gastrointestinal GVHD, 19-44 days posttransplant. There were simultaneous and uniform changes in the stomach through the small bowel consisting of thickened or flattened mucosal folds, thickening of the bowel wall, rapid transit, and excess luminal fluid. (2) Subacute phase-17 examinations were performed 13-96 days after the onset of gastrointestinal GVHD (40-118 days posttransplant). Abnormalities similar to those of the acute phase were noted, often with a striking segmental distribution. (3) Resolution phase-three patients, who earlier had sequential examinations, were studied when GVHD was no longer clinically active, 43-46 days after the onset of gastrointestinal GVHD (52-94 days posttransplant). These examinations showed improvement, with no abnormalities or effacement of mucosal folds. Mural thickening was confined to the terminal ileum. Gastrointestinal GVHD resolved in the three survivors; it persisted until death in nine of 13. The pathogenic mechanisms and differential diagnosis of the radiographic abnormalities are discussed.

Adolescent↗
PubMed1981

Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression.

Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases. Thirteen patients with extensive disease (group I) were not treated and only 2 survive with Karnofsky scores >- 70%. Mortality resulted from infections and morbidity from sica syndrome, pulmonary and hepatic insufficiency, scleroderma-like skin disease, and contractures. Another 13 (group II) received a median of 8 mo prednisone and/or a brief course of antithymocyte globulin, and 3 survive without disability. The other 21 (group III) were treated with a combination of prednisone (1.0 mg/kg/q.o.d.) and either cyclophosphamide, procarbazine, or azathioprine (all 1.5 mg/kg/day) for a median of 13 mo. Combination therapy was well tolerated with only modest myelotoxicity. Fifteen in group III had a good and 4 a fair response to treatment while 2 with no response died. Azathioprine and prednisone was the most effective regimen. All therapy has been discontinued in 12 group III patients: GVHD returned in 5 (including 2 who died in spite of retreatment) while 7 remain free of GVHD for a median of 11 (range 6-30) mo observation. Only I group III survivor is disabled and 16 of the original 21 are alive 2-4 yr after transplant with Karnofsky scores of 70%-100%. Thus, combination immmunosuppression appears to favorably affect and, in some cases, premanently arrest the adverse natural course of extensive chronic GVHD.

Antilymphocyte Serum↗