Mycobacterium tuberculosis infection in allogeneic bone marrow transplantation patients.

Bone marrow transplant (BMT) recipients are prone to bacterial, viral and fungal infections. Mycobacterium tuberculosis infection can occur in these patients, but the incidence is lower than that of other infections. This report describes four patients with Mycobacterium tuberculosis infection identified from 641 adult patients who received a BMT over a 12-year period (prevalence 0.6%). The pre-transplant diagnosis was AML in two patients and CML in the other two. Pre-transplant conditioning consisted of BU/CY in three patients and CY/TBI in one. Graft-versus-host disease (GVHD) prophylaxis was MTX/CsA in three patients and T cell depletion of the graft in one patient. Sites of infection were lung (two), spine (one) and central nervous system (one). Onset of infection ranged from 120 days to 20 months post BMT. Two patients had co-existing CMV infection. One patient had graft failure. The two patients who received anti-tuberculous (TB) therapy recovered from the infection. Although the incidence of tuberculosis in BMT patients is not as high as in patients with solid organ transplants, late diagnosis due to the slow growth of the bacterium can lead to delay in instituting anti-TB therapy. A high index of suspicion should be maintained, particularly in endemic areas.

Secondary acute myeloid leukemia 4 years after the diagnosis of hairy cell leukemia: case report and review of the literature.

A 49-year-old man diagnosed with hairy cell leukemia (HCL) achieved a complete remission lasting 4 years after treatment with cladrabine and subsequently developed acute myeloid leukemia. Although a wide variety of second malignancies have been noted in HCL with an incidence of 8.7%, acute myeloid leukemia (AML) has been reported only once previously in a splenectomized patient who had been treated with alpha interferon.

Urinary excretion and pharmacokinetics of acrolein and its parent drug cyclophosphamide in bone marrow transplant patients.

The urinary excretion and pharmacokinetics of acrolein (ACRO) and its parent drug cyclophosphamide (CP) were investigated in 16 randomly selected bone marrow transplant (BMT) recipients when CP was used for conditioning. Patients suffering from aplastic anemia (n = 3) received a 4-day course of CP at a dose of 50 mg/kg daily infused intravenously (i.v.) over 1 h. Patients with leukemia (n = 13) were given either a combination of busulphan followed by CP at a dose of 50 mg/kg infused i.v. over 1 h for 4 days, or CP at a dose of 60 mg/kg by i.v. infusion over 1 h daily for 2 days followed by total body irradiation. Serial plasma samples and urine were collected after the start of the first CP dose. CP was analyzed by capillary gas chromatography, whereas ACRO was measured in urine by liquid chromatography. The plasma concentration-time data for CP conformed to the two-compartment model and the mean and s.e.m. values of alpha, beta, Vss, total clearance, and renal clearance observed were 1.29 (0.31) h(-1), 0.17 (0.03) h(-1), 0.67 (0.13) l/kg, 0.14 (0.02) l/h x kg, and 0.0188 (0.0052) l/h x kg, respectively. The mean and s.e.m. values of fraction of CP excreted in the form of ACRO during this interval (fmu) and ratio of the 24-h urinary concentration of ACRO/creatinine (Cmu(n)) were 1.96 (0.35%) and 9.11 (2.19) microg of ACRO/mg of creatinine, respectively. Two patients developed hemorrhagic cystitis (HC). Each of these two patients excreted significantly (P < 0.01) more ACRO in the first and second 4-h urine collection periods. However, there was no significant difference in fmu or Cmu(n) of ACRO between either of these two patients and the rest. This suggests that the rate of appearance of ACRO in urine is more crucial for developing HC than the cumulative amount excreted.

Bone marrow mononuclear cell count does not predict neutrophil and platelet recovery following autologous bone marrow transplant: value of the colony-forming unit granulocyte-macrophage (CFU-GM) assay.

The common use of the marrow autograft mononuclear cell (MNC) count derives from positive correlative studies following allogeneic transplantation and from earlier conflicting data regarding the value of the bone marrow autograft colony-forming unit granulocyte-macrophage (CFU-GM) assay for prediction hematologic recovery after ABMT. We conducted a retrospective analysis at our institution to determine whether autograft CFU-GM levels predict engraftment of neutrophils and platelets after ABMT in heavily pretreated patients with hematologic malignancies. Between 1 January 1993 and 1 March 1995, 58 heavily pretreated patients received only marrow cells as the autograft product. Patients with Hodgkin's disease (n = 25), acute myeloid leukemia (n = 19), and non-Hodgkin's lymphoma (n = 14) underwent intensive therapy with etoposide and melphalan. Unpurged marrow containing a minimum of 1.5 x 10(8)/kg (range: 1.5-4.8) was infused. Median time to an absolute neutrophil count > or = 0.5 x 10(9)/L was 21 days (range 10-270) and median time to a platelet count > or = 20 x 10(9)/L independent of transfusions was 44 days (range 13-317). There was no correlation between autograft MNC count and neutrophil or platelet engraftment. However, a correlation between autograft CFU-GM and both platelet and neutrophil recovery was demonstrated with a threshold CFU-GM of 3 x 10(4)/kg; delayed neutrophil recovery was observed in 79% of patients below this threshold compared to only 9% in those with an autograft CFU-GM level of more than 3 x 10(4)/kg (p = 0.0001). Similarly, platelet recovery was delayed in 76% of patients below, and 20% of those above this threshold (p = 0.003). We conclude that marrow autograft CFU-GM is predictive of engraftment of both platelets and neutrophils in heavily pretreated patients after ABMT for hematological malignancies.

Abnormal thyroid stimulating hormone (TSH) levels in adults following allogeneic bone marrow transplants.

Thyroid function abnormalities in 270 adult patients post-BMT are described. Various conditioning regimens were used and the effects of three TBI and one chemotherapy only based regimens are compared. The overall incidence of elevated TSH is 8.9; 3.8, 7.2 and 16.7% in those patients who received 300, 500 and 1200 cGy respectively and 11.7% in those who received BuCy conditioning. Three cases (1.1%) of clinial hypothyroidism were observed. Compensated hypothyroidism defined as an elevated TSH in the presence of normal T3, T4 levels and transient in some cases, was the most common finding. All but four cases occurred in the first 2 years after BMT. In the remaining four, three occurred in patients with chronic GVHD. The results reported here show a lower prevalence than observed in most other reviews, particularly for children. A trend was observed with increasing radiation doses. The results are not significantly different from those we observed in the BuCy regimen.

Primary bilateral adrenal lymphoma.

We report a case of primary bilateral adrenal non-Hodgkins lymphoma (NHL), with hypercalcemia at the time of presentation. Medical literature review showed that this is an extremely rare site for lymphoma, but presents a distinct clinical entity with many features that differ from NHL overall, extranodal NHL, and NHL in other endocrine organs. The diagnosis is frequently not suspected antemortem, and long delays between the onset of symptoms and the diagnosis are frequent. Adrenal insufficiency is also common, and may be a lethal complication of these tumors. Response to therapy and survival are extremely poor.

Granulomatous oesophagitis: a case of tuberculosis limited to the oesophagus.

In this paper we report on a 31-year-old Saudi male with tuberculosis limited to the oesophagus, presenting with dysphagia. Radiological examination revealed oesophageal ulceration with diverticulum formation. The diagnosis of oesophageal tuberculosis was made only after endoscopy and histopathological examination. The patient gained weight and became symptomless after three months of chemotherapy with antituberculous drugs. The rarity of such a presentation prompted this case report.