Adverse haematological complications of anticancer drugs. Clinical presentation, management and avoidance.

Haematological complications frequently occur in patients treated with chemotherapeutic agents. The degree and duration of bone marrow suppression depends upon the type of agent used. In general, agents that are cell cycle phase-specific tend to cause early myelosuppression with rapid marrow recovery, as compared to the non-phase-specific agents. Host factors including patient age, nutritional status, marrow infiltration or damage, and hepatic and renal function also affect haemotoxicity. Chemotherapeutic agents suppress proliferating or potentially proliferating precursors of neutrophils, platelets and red blood cells to the same extent. With most drugs, neutropenia tends to be dose limiting and more severe than thrombocytopenia. Because of the longer life span of red blood cells, severe anaemia is rarely a problem. The management of myelosuppression is multifaceted, and consists of aggressive antibiotic therapy to treat or prevent the infections that occur with neutropenia, as well as red blood cell and platelet transfusion support to correct anaemia and prevent bleeding. The role of the haemopoietic growth factors including erythropoietin, colony-stimulating factors and the interleukins is currently being evaluated in clinical trials. Haemolytic uraemic syndrome, haemolytic anaemia and therapy-induced myelodysplasia and/or acute leukaemia are uncommon and potentially severe complications of chemotherapeutic agents.

Disseminated histoplasmosis in patients with AIDS.

Disseminated histoplasmosis (DH) is recognized as an opportunistic infection in patients with the human immunodeficiency virus (HIV), especially in regions where histoplasmosis is endemic. At the Kansas University Medical Center 148 patients were hospitalized with the diagnosis of AIDS from December 1983 to March 1991; 23 of these patients (16%) had disseminated histoplasmosis. The charts of these 23 patients were reviewed. Clinical signs and symptoms included fever (91%), cough (65%), and weight loss (48%). Splenomegaly, hepatomegaly, or lymphadenopathy was present in 52% of all patients. Anemia (39%), leukopenia (65%), and thrombocytopenia (52%) were common, and 22% had pancytopenia. Diagnosis was made by peripheral smear examinations (organisms visualized on 7 of 22 smears [32%]), blood cultures (positive for H capsulatum in 16 of 20 patients, [80%]), bone marrow cultures (positive in 14 of 15 patients, [93%]), and bone marrow aspirate and biopsy examinations (organisms seen on 18 of 21 stains, [86%]). The combination of these four tests revealed the diagnosis of DH in 23 of 23 patients (100%). Induction and maintenance amphotericin B therapy was given to all but 2 patients, and currently 8 of the 23 are alive. DH is a common opportunistic infection in AIDS patients from regions endemic for histoplasmosis. When DH is suspected, a peripheral smear examination, blood cultures, bone marrow cultures and bone marrow aspirate and biopsy should be done to make the diagnosis, since suppression of the disease is possible with appropriate therapy.

Use of blood components in cancer patients with bleeding.

The need for blood components for oncology patients is small compared with the need for patients with hematologic malignancies. The subject is important because use of these valuable components is dependent on a limited supply and availability. Agreement on when to use components is extremely important. In fact, at the time of this writing, the Transfusion Practices Committee of the American Association of Blood Banks is conducting an extensive survey on the use of platelets in oncology and hematology cancer patients (Questionnaire on Institutional Policy on Platelet Transfusion Practice for Hematology/Oncology Patients). The results will, we hope, provide a consensus on the proper times and counts that require prophylactic use of components for these patients. Because these patients use the vast majority of components (see Table 15), their proper use is imperative to maintaining an adequate platelet and frozen plasma supply. Transfusion support in cancer patients is vital for their survival. Platelets, in particular, are necessary to prevent serious bleeding. The risks from transfusion must always be considered. Fortunately, with increased monitoring of the blood supply, they have been reduced. As with any therapeutic regimen, these risks must be weighed against the benefit the patient may gain. Transfusion should always be used prudently.

Use of platelets and other transfusion products in patients with malignancy.

The need for blood components for oncology patients is small compared with the need for patients with hematologic malignancies. Appropriate use of blood components is necessary, not only medically, but also because of limited supply and availability. Agreement on when to use components is extremely important. In fact, at the time of this writing, the Transfusion Practices Committee of the AABB is conducting an extensive survey on the use of platelets in the oncology and hematology cancer patients (Questionnaire on Institutional Policy on Platelet Transfusion Practice for Hematology/Oncology Patients). The results will, it is hoped, provide a consensus on the proper times and counts that require prophylactic use of components for these patients. Since these patients use the vast majority of components (see Table 15), their proper use is imperative to maintaining an adequate platelet and frozen plasma supply. Transfusion support in cancer patients is vital for their survival. Platelets, in particular, are necessary to prevent serious bleeding. However, refractoriness to platelet transfusions can develop. It must be appreciated that refractoriness is not a general problem and need not require the expensiveness of a universal decision for handling all platelet transfusions in the same manner. Total refractoriness probably occurs in 15 to 20% of patients frequently transfused. In patients in whom frequent platelet transfusion is anticipated, that is, bone marrow transplantation, the development of platelet refractoriness may be reduced by using SDPC and administering them through leukocyte filters. Patients who become refractory to either random or SDPC can either be cross-matched for single-donor platelets that are compatible or can be given HLA-A,B matched platelets. Certainly, the success of platelet transfusion in leukemic patients cannot be denied, since only a small number of these patients now die because of bleeding due to platelet refractoriness. Most of the serious bleeding still seen is associated with sepsis. The risks from transfusion must always be considered. Fortunately, with increased monitoring of the blood supply, they have been reduced. As with any therapeutic regimen, these risks must be weighed against the benefit the patient may gain. Transfusion should always be used prudently.

Therapy of aplastic anemia with sequential antithymocyte globulin and cyclosporin.

Five consecutive patients with severe aplastic anemia were treated with antithymocyte globulin followed by cyclosporin A. All received antithymocyte globulin initially, and because of lack of response within a 4 week period, cyclosporin was administered subsequently. Hematologic improvement occurred within four months of initiation of cyclosporin. Four patients no longer require blood product support, while one remains transfusion-dependent. In two patients, thrombocytopenia developed when the cyclosporin was tapered but re-institution of the drug resulted in a prompt improvement of counts. These observations indicate that the sequential use of antithymocyte globulin and cyclosporin may be an effective therapeutic approach in the treatment of severe aplastic anemia.

Leukocyte depletion filters: a comparison of efficiency.

Four commercially available leukocyte depletion filters were evaluated using a flow cytometric technique to determine the efficiency of each type of filter. The Sepacell R-500A and the PALL RC50 were the most efficient in leukocyte depletion having a mean depletion percentage of 99.3% and 99.5%, respectively. The PALL RC100 which is used for two units also had a 99.3% depletion with the first unit but with the second unit the depletion dropped to 94.2%. The imugard IG-500 had a 97.3% depletion. Red cell recovery ranged from 87.4% for the PALL RC50 to 92.2% for the Sepacell R-500A.

Primary hypercoagulable states in general and vascular surgery.

Primary hypercoagulable states are increasingly recognized as causes of venous and arterial thromboembolism in surgical patients. Herein, we describe 10 patients with this syndrome who were diagnosed during a recent 1-year period. A family history and past medical history of thromboembolism and an unusual site of thrombosis are emphasized for accurate diagnosis. Although antithrombin III deficiencies were the most common abnormality found, we describe three patients with hypofibrinolytic syndromes and increased levels of tissue plasminogen activator inhibitor. The effectiveness of anticoagulation therapy in preventing recurrent thromboembolism is stressed.

A flow cytometric technique to accurately measure post-filtration white blood cell counts.

Leukocyte-depleted blood products are being used with increasing frequency in hopes of preventing or delaying platelet alloimmunization. However, accurately monitoring the efficiency of leukocyte (WBC) removal is a difficult problem because electronic cell counters are not accurate at very low WBC numbers and hemocytometer counts are tedious and time consuming. A simple flow cytometric technique was developed which accurately and rapidly measures extremely low WBC counts. Using a propidium iodide solution which causes DNA to fluoresce, the residual WBC count was measured in 42 units of blood products after leukocyte depletion using a commercial filter. There was a significant correlation with simultaneous hemocytometer counts, r = 0.672, but residual WBC could be identified in every unit using the flow cytometer, whereas in 19% of the units no WBC were seen using the hemocytometer. Extremely low counts, as low as a single WBC/4 microliters could be reproducibly obtained. In addition, serial dilution studies yielded a correlation coefficient of 0.997. Because most clinical laboratories now have access to flow cytometers, this technique can be widely used.

Malignancy-induced lactic acidosis.

Lactic acidosis, a rare and usually fatal complication of malignancy, is defined as a clinical condition in which the pH is less than or equal to 7.35 and the serum lactate level greater than or equal to 5 mEq/L. We have described the clinical aspects of four cases of lactic acidosis associated with malignancy, and have reviewed all reported cases of lactic acidosis in malignancy meeting the criteria. Rapid recognition of the condition and prompt institution of chemotherapy led to reversal of lactic acidosis in three of our four patients, but long-term survival is related to the responsiveness of the underlying tumor.

Flow cytometric measurement of antiplatelet antibodies.

A flow cytometric technic was developed to detect platelet surface-bound immunoglobulin in patients with thrombocytopenia. Elevated platelet surface IgG and/or IgM was detected in 90.9% of patients with immune thrombocytopenia purpura (ITP). False positive results occurred in 9.3% of patients with nonimmune thrombocytopenia usually associated with sepsis. False negatives occurred most frequently in adults with chronic ITP. Measurement of platelet surface immunoglobulin with this flow cytometric technic helps differentiate immune from nonimmune thrombocytopenia.

Detection of platelet alloantibodies by flow cytometry. Characterization and clinical significance.

A flow cytometric technic was developed to detect platelet alloantibodies in patients who had received multiple platelet transfusions. All clinically alloimmunized patients had IgG alloantibodies, whereas the nonalloimmunized patients were within the range of the normal controls. There was a negative correlation between the IgG level and the platelet increment. IgM and IgA alloantibodies also were detected in some patients. When they were present in addition to IgG, the platelet increment appeared to be reduced further.

Pathogenicity of Candida paratropicalis.

A new Candida species, Candida paratropicalis, was recently described. Four cases of infections due to C paratropicalis are reviewed in detail and an additional five cases are reviewed to establish the clinical relevance of this species of yeast. Candida paratropicalis was isolated from blood and several other body sites. Although the isolates tested were sensitive in vitro to amphotericin B and fluocytosine, significant morbidity and mortality were associated with the infections.

Profound neutropenia associated with benzylpenicillin.

A 31-year-old white man with suspected aspiration pneumonia complicated by multiple pulmonary abscesses had profound neutropenia during a course of high-dose benzylpenicillin therapy for suspected bacterial endocarditis. Antigranulocyte antibodies were identified in the patient's serum. Leukopenia is an uncommon but potentially serious complication of therapy with this drug. We recommend weekly monitoring of blood counts during prolonged therapy with any beta-lactam antibiotic.

Central nervous system involvement in mycosis fungoides: diagnosis, treatment and literature review.

A 58-year-old man with mycosis fungoides developed headache, back pain, and dorsal column signs. A diagnosis of central nervous system (CNS) involvement by mycosis fungoides was made on examination of his spinal fluid. In this patient, cranial and local radiotherapy and aggressive treatment with intrathecal methotrexate cleared the leukemic cells from his CNS, and maintenance therapy with intrathecal methotrexate has resulted in an 18-month remission.