Treatment of leukemia with partially matched related bone marrow transplantation.

The results of partially matched related donor (PMRD) marrow transplantation for 82 patients with leukemia are reported, including 45 who received two antigen disparate grafts. Following intensive radiochemotherapy, patients received grafts which were partially depleted of T cells by the monoclonal antibody T10B9 and complement. Actuarial probability of engraftment was 86% (95% CI = 78-93%). The median day to engraftment was similar among recipients of grafts disparate at one, two or three antigen loci. The incidence of severe (grades III and IV) acute graft-versus-host disease and extensive chronic graft-versus-host disease was 13% and 6%, respectively. The probability of disease-free survival for the entire cohort of patients is 31% at 3 years. Age < or = 30 years, early or intermediate stage disease and a graft disparate at one or two loci predicted longer disease-free survival in multivariant analysis. Moreover, 47% of patients receiving PMRD grafts disparate at two loci who had both these favorable pretransplant characteristics were alive and free of disease 3 years after transplantation. We believe that the utilization of PMRDs, especially those with two antigen disparate grafts, can extend allogeneic transplantation to additional leukemic patients lacking a histocompatible donor, with acceptable results.

Allogeneic bone marrow transplantation with T cell-depleted partially matched related donors for advanced acute lymphoblastic leukemia in children and adults: a comparative matched cohort study.

Allogeneic BMT provides the best treatment currently available for long-term disease-free survival in patients with recurrent ALL. Historically, partially matched related donors provided the opportunity for treatment to a greater number of patients than matched related donors at the expense of decreased overall survival. In this study we compare the results in recurrent ALL patients transplanted with either HLA identical sibling bone marrow or partially matched related bone marrow. Thirty-two patients with relapsed ALL received partially matched bone marrows from a relative with one to three HLA, A, B and Dr antigen mismatches. Bone marrow was partially T cell-depleted with murine T10B9.1A-31 moAb. Sixteen patients with relapsed ALL received HLA-matched sibling bone marrows. All partially matched patients received additional GVHD prophylaxis with methylprednisolone in addition to anti-CD5 immunotoxin and/or CYA. All matched patients in addition to methylprednisolone received MTX and/or CYA. We observed no difference in disease-free survival between patients transplanted with partially matched bone marrow (median follow-up 1252 days, range 778-2035 days) vs those transplanted with HLA-matched bone marrow (median follow-up 1472 days, range 1165-2800 days; P = 0.48). Median survival for all patients is 38% (95% CI 24-52%) at 6 years. Patients transplanted in remission had a significant increase in disease-free survival when compared to those in relapse (P = 0.007). Our data suggest that partially matched BMTs from related donors are a comparable alternative to fully matched transplants in patients with ALL.

Proliferation of abnormal bone marrow histiocytes, an undesired effect of granulocyte macrophage-colony-stimulating factor therapy in a patient with Hurler's syndrome undergoing bone marrow transplantation.

Granulocyte macrophage-colony-stimulating factor (GM-CSF) has shown promise as a means of alleviating leukopenia associated with a wide variety of disorders. It is currently undergoing evaluation as an adjunct to bone marrow transplantation but its use in patients with metabolic disorders, such as Hurler's syndrome (HS), has not been explored. We followed bone marrow morphology in a 2-year-old male with HS who received up to 8 micrograms/kg GM-CSF per day because of failure of allogeneic bone marrow engraftment. Both premortem and postmortem bone marrow sampling revealed almost complete replacement of the marrow space by sheets of histiocytes demonstrating metachromatic cytoplasmic granules. Such cells were present in far greater numbers than are usually seen in untreated patients with HS or patients with HS undergoing successful bone marrow transplantation without GM-CSF. Moreover, the in vitro culture of bone marrow from a second HS patient showed a GM-CSF dose-related increase in colony formation up to a dose of 250 units/ml. Microscopic examination of these colonies showed a high percentage of histiocytes identical to those seen in the patient's bone marrow. These observations suggest that caution should be exercised when considering administration of CSFs to patients with HS and similar metabolic storage diseases.

Mycobacterial infection after renal transplantation--report of 14 cases and review of the literature.

During a nine-year period, 14 cases of mycobacterial infection (tuberculosis) developed in 403 renal transplant recipients at the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, an incidence of 3.5 per cent. The annual incidence of tuberculosis was about 50 times higher than that in the general population. Infection was disseminated in nine (64.3 per cent), pulmonary in four (28.6 per cent), and genitourinary in 1 (7.1 per cent). In one patient tuberculosis was transmitted by the donor's kidney. The clinical manifestations were often ill-defined and not different from that in the normal host. Cultures from all patients grew Mycobacterium tuberculosis; concomitant infection with other organisms was present in five patients (35.7 per cent). Two of 18 patients (group 1) with positive pretransplant tuberculin skin test developed tuberculosis after transplantation (11 per cent), and neither received isoniazid prophylaxis; three of 70 patients (group 2) with negative skin tests developed tuberculosis after transplantation (4.3 per cent). The difference between the two groups was not statistically significant. Review of all published cases of mycobacterial infections in renal transplant recipients revealed 130 cases. Tuberculosis was disseminated in 38.7 per cent, pulmonary in 40.2 per cent, cutaneous in 12 per cent, and miscellaneous in 9.4 per cent. Atypical mycobacteria were responsible for 29 per cent of disseminated infections, 8 per cent of pulmonary infections and all cases of cutaneous and articular tuberculosis. Invasive procedures were needed to establish the diagnosis in 21 of 33 disseminated cases but in only three of 47 cases of pulmonary tuberculosis (p less than 0.0001). The mortality rate from disseminated disease was 37 per cent and from all other forms of tuberculosis was 11 per cent (p less than 0.005). These findings (1) confirm the higher incidence of tuberculosis in renal transplant recipients, compared to the general population; (2) suggest that pretransplant skin testing probably has little value in identifying patients at risk; (3) show that disseminated tuberculosis is common after renal transplantation and requires invasive procedures for diagnosis; (4) confirm that the donor kidney may be an important source of infection; and (5) indicate that concomitant infection with other organisms is common.

The value of prophylactic antibiotics during the insertion of long-term indwelling silastic right atrial catheters in cancer patients.

Over a 3.5 year period from August 1982 to December 1985, 200 Hickman catheters (Evermed, Medina, WA) were inserted into patients at the King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh, Saudi Arabia. One hundred sixty catheters were placed in patients with malignant disease, many of whom were immunosuppressed at the time of catheter insertion. Seventy of 160 (44%) patients received prophylactic antibiotics and 90 (56%) did not. The mean age of each group was 23 years (range, 2 to 70 years), and the patients in each group were statistically similar in sex, underlying disease, and routine preoperative hematologic and biochemical evaluation. Exit-site wound infections occurred in 50 of 90 (55.5%) patients who did not receive prophylaxis and in 12 of 70 (17%) patients who received prophylaxis (P less than 0.0001). There was no statistically significant difference in the incidence of tunnel and incision site infections. The mean duration of antibiotic prophylaxis was 2.9 days (SD, 1.2 days). Organisms cultured from catheter associated infections, included Staphylococcus epidermidis 36, S. aureus 30, Klebsiella pneumoniae 1, Pseudomonas aeruginosa 3, Escherichia coli 1, and diphtheroids non-CDC-JK 3. Vancomycin was used as antibiotic prophylaxis in 64 patients, Kefzol (Eli Lilly, Indianapolis, IN) in one, oxacillin in three, nafcillin in one, and Septra (Burroughs Wellcome, Research Triangle Park, NC) in one. The data indicate that the use of intravenous antibiotic prophylaxis significantly reduces exit site infection and may reduce both tunnel and incision site infection. Prophylactic antibiotic coverage should be provided to patients during insertion of long-term indwelling right atrial catheters.

Brucella endocarditis.

Brucella endocarditis is an underdiagnosed, fatal complication of human brucellosis. Four successfully treated cases of Brucella endocarditis are reported. The development of a new valvar lesion and bulky vegetations seen on echocardiography helped to identify Brucella endocarditis occurring during systemic brucellosis. The aortic valve was affected in all four patients, and in one the mitral valve was also affected. Medical treatment did not cure the patients and all needed valve replacement--for haemodynamic deterioration in three and because a further embolism was feared in one. Antibiotics were continued for six to nine months after operation. There was no early or late mortality and no recurrence after a follow up of 15 months.

Nervous system brucellosis: diagnosis and treatment.

We treated six patients with nervous system brucellosis causing polyradiculitis (2 patients), myelopathy (2), encephalitis (1), or meningitis (1). Diagnosis was based on Brucella species cultured from one patient, and a twofold or greater rise in antibody titer after therapy was started in the others. Treatment with trimethoprim-sulfamethoxazole with rifampin (5 patients) or tetracycline (1 patient) produced excellent clinical and laboratory response.

Acquired immune deficiency syndrome in the Middle East from imported blood.

In Saudi Arabia, a native patient with no known risk factors for the acquired immune deficiency syndrome (AIDS) developed both clinical and laboratory evidence of AIDS 2 years after receiving transfusion of 11 units of blood obtained from a commercial distributor in the United States. This case suggests that a history of transfusions of blood components imported from areas where AIDS is prevalent should be elicited from patients in the Middle East with symptoms and physical findings suggesting AIDS.

Management of anaerobic infections.

Anaerobic infections are reviewed with emphasis on management. Most anaerobic pulmonary infections respond to penicillin G, even when Bacteroides fragilis (penicillin-resistant) is present. Clindamycin is suitable in penicillin-sensitive patients. Intraabdominal infections have a complex flora usually involving anaerobes, especially B. fragilis. It is desirable to use antimicrobial therapy to cover potential pathogens of all types. Surgical drainage and debridement are extremely important considerations. Anaerobic bacteria were found in 72% of 200 patients with female genital tract infections and were the exclusive isolates in 30%. Surgical therapy is primary, but antimicrobial and anticoagulant therapy are also important. A variety of soft-tissue infections involve anaerobes. Surgery is the major therapeutic approach. Anaerobic endocarditis is uncommon but may be difficult to manage. Chloramphenicol is ordinarily the drug of choice for brain abscess. New antimicrobial agents, which are under investigation and are promising, include new penicillins, new cephalosporins, new tetracyclines, and metronidazole.

Treatment of fungal infections with flucytosine.

Treatment with flucytosine of 20 patients with fungal infections gave favorable results in four patients with crytococcal infections, two of four patients with disseminated candidiasis, eight of ten patients with urinary tract infections due to Candida albicans and Torulopsis glabrata, and tow of three patients with miscellaneous infections due to Calbicans. Two patients with crytococcal meningitis and altered host resistance and one patient with an aorto femoral graft infection due to C albicans were treated with flucytosine and smphotericin B. The infection was eradicated in one of the patients with meningitis, and cultures from an infected arterial graft became negative. Adverse side effects of flucytosine included mild leukopenia and thrombocytopenia, a transient increase in alkaline phosphatase and glutamic oxaloacetic transaminase, and nausea and diarrhea.