Prospective audit of cytomegalovirus-negative blood product utilization in haematology/oncology patients.

The transfusion management of immunocompromised patients often requires special blood product use such as cytomegalovirus (CMV)-negative cellular products, which are more costly than standard blood products and occasionally in short supply. We audited the use of CMV-negative products in haematology/oncology patients to determine the appropriateness of their use. A concurrent-prospective audit was conducted of all orders for CMV-negative packed red blood cell (PRBC) and platelet products in 201 haematology/ oncology patients. Once CMV serostatus was determined, orders for inappropriate CMV-negative units were cancelled, and filled as CMV untested units. During the 21-month period of this audit, the rates of inappropriate transfusions decreased for PRBC from 73.2% to 14.3% (chi2 = 68.4, P<0.001) and for platelets from 68.1% to 10.6% (chi2 = 65.6, P<0.001). The median time to cancellation of inappropriate CMV-negative orders was 11 days. This audit resulted in estimated cost savings of $16500 over the 21-month duration. Inappropriate requests for scarce and expensive blood products are substantially reduced by concurrent-prospective auditing of transfusion practice, in a manner that is both simple and cost effective.

Counseling sexually active teenagers treated with potential human teratogens.

Adolescents with hemoglobinopathies need daily chelation therapy with drugs which are known or suspected to be teratogenic. The prevention of fetal exposure to such drugs is therefore a major task for health professionals caring for these patients. We describe a pilot program aiming to prevent pregnancy among sexually active adolescents treated with iron chelators in Toronto. Most of them had normal response to GnRH, suggesting endocrinologic fertility, and unlike the literature concerning their healthy peers, all sexually active patients in this study reported use of at least one form of contraception.

Desferrioxamine ototoxicity in an adult transfusion-dependent population.

OBJECTIVE: The purpose of this study was to identify the incidence of hearing loss in a population of 75 adult (19-68 years old) transfusion-dependent patients with thalassemia major, sickle cell disease, Diamond-Blackfan anemia, and various other hematologic disorders treated with regular transfusion schedules. Ninety-three percent (70/75) of patients had a history of long-term subcutaneous or intravenous desferrioxamine therapy. METHODS: The patients underwent routine otolaryngologic history and physical examination, along with standard pure-tone audiometry at 250, 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz, with hearing loss defined as 25 dB or greater at one or more frequencies. RESULTS: Hearing loss was present in 57% (43/75) of patients. More importantly, hearing loss attributable to desferrioxamine ototoxicity was present in 29% (22/75) of patients. Sixteen patients treated previously with desferrioxamine were switched to the experimental oral chelating agent, L1. Eight of these 16 patients had hearing loss attributable to desferrioxamine, with 5 of these patients worsening with the experimental oral chelating agent L1. Seventy-nine percent (59/75) of patients were thalassemic. Fifty-four percent (33/59) of these thalassemic patients had hearing loss. However, 35% (21/59) of the thalassemic patients had hearing loss attributable to desferrioxamine ototoxicity. All thalassemic patients with desferrioxamine ototoxicity had high-frequency sensorineural hearing loss, with 33% (7/21) having a notch at 6 kHz. In addition, 5% (1/21) had notching at 3 khz. Few of the hearing losses were disabling. CONCLUSIONS: Management of these patients requires proper dosing of desferrioxamine and transfusion therapy, along with regular monitoring of body iron burden and hemoglobin. In addition, regular otolaryngologic and audiometric follow-up with special care to include the frequencies of 3 and 6 kHz may help recognize and prevent permanent ototoxicity.

Severity of beta-thalassemia due to genotypes involving the IVS-I-6 (T-->C) mutation.

Among individuals of Mediterranean or Middle Eastern descent, the IVS-I-6 (T-->C) mutation is one of the most common causes of beta-thalassemia. In this report, we describe the clinical phenotypes of a group of beta-thalassemia patients who are compound heterozygotes for the relatively mild IVS-I-6 (T-->C) beta-thalassemia mutation and more severe beta(+)- or beta (0)-thalassemia mutations. Although most of these patients are transfusion-dependent, the requirement for regular transfusions generally occurred late in childhood. A correlation between concomitant alpha-thalassemia and a mild transfusion-independent phenotype is not apparent, indicating the involvement of other ameliorating determinants.

Treatment outcomes in patients with adult thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.

BACKGROUND: Plasma treatment has improved the outcomes in adults with thrombotic thrombocytopenic purpura (TTP)-hemolytic uremic syndrome (HUS). We reviewed our experience in treating unselected patients to determine the clinical outcomes and to evaluate the treatments given in addition to plasma. METHODS: A chart review of all cases of TTP and HUS in adults treated at the Toronto (Ontario) Hospital, the largest treatment center for adults with TTP-HUS in the province of Ontario, was conducted. RESULTS: Sixty-seven episodes of TTP-HUS in 52 consecutive adult patients were treated during a 12-year period. Plasma was the primary form of therapy, and most patients received plasma exchange. A complete hematologic remission was achieved in 65 of 67 episodes; however, two patients in remission were brain-dead. The time to complete remission varied from 3 to 58 days (median, 13 days). The death rate during the acute illness was 8%. Long-term sequelae included relapses, persisting renal impairment, hepatitis, and transfusion-associated acquired immunodeficiency syndrome. Relapses occurred in 21% of patients during a median follow-up of 1.1 years (range, 0.1 to 18 years). Analyses of the treatment given in addition to plasma did not demonstrate a significant benefit in terms of reducing the illness duration, mortality, or long-term sequelae. CONCLUSION: While most patients recovered from TTP-HUS, deaths still occurred and many patients suffered long-term complications. The role of the treatments given in addition to plasma is uncertain.

Clinical course and molecular characterization of a compound heterozygote for sickle hemoglobin and hemoglobin Kenya.

We describe a 25-year-old black woman who presented with a long history of anemia requiring transfusions during childhood and adolescence. Molecular analysis revealed her to be a compound heterozygote for the sickle mutation and the approximately 22.7 kb deletion associated with hemoglobin Kenya. This patient's clinical course was more severe than previously reported for the Hb S/Hb Kenya genotype, a probable consequence of concomitant iron deficiency.

Reduction in tissue iron stores with a new regimen of continuous ambulatory intravenous deferoxamine.

A new regimen of 24-hr ambulatory continuous intravenous infusion of deferoxamine (CIV DFO) through central venous ports was instituted in nine patients aged (mean +/- SD) 22.4 +/- 5.8 years over a period of 15.7 +/- 7.3 months. Central venous infusion sites were changed weekly in the clinic, eliminating the necessity for reconstitution of DFO and needle insertion at home. Because CIV DFO could be interrupted only by medical personnel, patient compliance was documented accurately; patients administered 93.0% +/- 3.2% of CIV DFO prescribed. Mean urinary iron excretion on CIV DFO (66.8 +/- 50.4 mg/24 hr) was significantly greater than that quantitated during 12-hr equivalent-dose subcutaneous DFO infusions (23.4 +/- 18.3 mg/24 hr; P less than 0.025). Mean serum ferritin declined by 71% over the treatment period (P less than 0.005). This regimen confers the advantages of uninterrupted exposure to DFO, is associated with excellent patient compliance, and should be considered in any patient with severe iron overload and erratic compliance with DFO.

Two novel beta-thalassemia mutations in the 5' and 3' noncoding regions of the beta-globin gene.

Two novel beta-thalassemia mutations are described. The first mutation, found in an Italian family, is a G----A substitution in nucleotide (nt) +22 relative to the beta-globin gene Cap site. This mutation creates a cryptic ATG initiation codon, the utilization of which for translation would result in premature termination 36 bp 3' downstream. The second mutation, found in an Irish family, is a T----C substitution in nt +1570, or 12 bp 5' upstream of the AATAAA polyadenylation signal in the 3' noncoding region. It is postulated that this mutation leads to destabilization of the encoded beta-globin mRNA.

Expansion of B lymphocytes with an unusual immunoglobulin rearrangement associated with atypical lymphocytosis and cigarette smoking.

Persistent polyclonal lymphocytosis has been described in a group of female patients who all have the HLA-DR7 antigen in common and who are all heavy cigarette smokers. Immunoglobulin heavy chain gene rearrangement was analyzed by hybridization with specific immunoglobulin heavy chain genes to restriction enzyme-digested genomic DNA samples. The results in two of these patients showed that the lymphocytosis was associated with an expanded subpopulation of B-lineage cells represented by the presence of an unusual immunoglobulin gene rearrangement pattern. Expansion of this subpopulation of B cells appeared to be linked to cigarette smoking since the intensity of the cell population harboring the rearranged gene was much stronger in patients who were smoking heavily compared with the same patients who were temporarily not smoking.

Chemotherapy following surgery for stages IE and IIE non-Hodgkin's lymphoma of the gastrointestinal tract.

Twenty-six patients were treated with chemotherapy following surgery for gastrointestinal non-Hodgkin's lymphoma (GI-NHL). The median age was 50 years (range, 20 to 76). The primary site included stomach (16 patients), small bowel (seven), large bowel (two), and mesenteric nodes (one). Following surgery, nine patients had macroscopic and four patients had microscopic residual disease, and 13 were felt to have had complete surgical resection. Thirteen patients were stage I and 13 were stage II. Sixteen patients were treated with COPP (cyclophosphamide, vincristine, procarbazine, prednisone), nine with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and one with CVP (cyclophosphamide, vincristine, prednisone). At a median follow-up of 50 months (8+ to 178+ months) ten of 12 stage I patients and nine of 14 stage II patients remain alive. Of the nine patients with macroscopic residual disease, four died of disease 6.5 to 11.0 months after diagnosis, and five are alive 8+ to 178+ months from diagnosis. Fourteen of the remaining 17 patients who had complete surgical resection are alive without disease. Death in the other three patients was due to multiple abdominal abscesses at 12 months, adenocarcinoma of the colon at 57 months, and dementia and progressive neurologic dysfunction at 65 months. No patient who had complete resection has relapsed or developed systemic disease after chemotherapy. These results suggest that complete surgical resection is an important prognostic factor and that chemotherapy without irradiation in completely resected localized GI-NHL can prevent local and systemic relapse resulting in long-term disease-free survival.