We studied the mechanism of platelet injury in 20 patients receiving heparin, three of whom became thrombocytopenic. Platelets from these three patients had increased levels of IgG and C3, which correlated with the presence of thrombocytopenia; their plasma caused the release of serotonin from normal platelets at concentrations of heparin within the usual therapeutic range. This reaction required IgG and an intact classic complement pathway. The 17 patients receiving heparin in whom thrombocytopenia did not develop had normal levels of platelet-associated IgG and C3. Plasma from 14 of these patients caused the release of serotonin, but only at heparin concentrations above the therapeutic range, in a reaction that also required IgG and complement. The addition of heparin to 15 normal plasma samples did not cause platelet injury in vitro. These studies indicate that heparin administration can be associated with complement-mediated platlet injury. The dose-dependent nature of this process may account for the occurrence of thrombocytopenia in some of these patients.

Summary:there was more rapid recovery of platelets in patients receiving the higher CD34 + cell doses. 4 Some patients receiving Ͻ2-2.5 × 10 6 CD34 + cells/kg have greatly Engraftment kinetics after high-dose chemotherapy (HDC) were evaluated in patients receiving autologous delayed platelet recovery as compared to patients receiving a higher cell dose. 3,5-7 peripheral blood stem cell (PBSC) infusions with a low CD34 ؉ cell content. Forty-eight patients were infusedIt has also been suggested that there are factors other than CD34 + cell dose involved in hematologic recovery with Ͻ2.5 ؋ 10 6 CD34 ؉ cells/kg; 36 because of poor harvests and 12 because they electively received only a after HDC and PBSC infusion. For example, in a series of 225 patients with multiple myeloma receiving HDC, the fraction of their harvested cells. A median of 2.12 ؋ 10 6 CD34 ؉ cells/kg (range, 1.17-2.48) were infused followinfusion of 2.0 × 10 6 CD34 + cells/kg resulted in rapid engraftment in patients who had received Ͻ6 months of ing one of seven different HDC regimens. All patients achieved absolute neutrophil counts у 0.5 ؋ 10 9 /l at a therapy with melphalan, but Ͼ5 × 10 6 CD34 + cells/kg were required for rapid platelet recovery in patients who had median of day 11 (range, 9-16). Forty-seven patients achieved platelet counts у 20 ؋ 10 9 /l at a median of day received Ͼ12 months of melphalan. 8 Target CD34 + cell doses of 2.5 or 5.0 × 10 6 /kg are easily 14 (range, 8-250). Nine of 47 (19%) had platelet recovery after day 21, 4/47 (9%) after day 100 and one died achievable in the majority of patients. [3][4][5] In a relatively small fraction of heavily pretreated patients, however, these on day 240 without platelet recovery. Twenty-six patients (54%) died of progressive disease in 51-762 cell doses are not obtainable. 3-5 Furthermore, sequential or tandem administration of HDC followed by the infusion of days; 22 (46%) are alive at a median of 450 days (range, 94-1844), 17 (35%) of whom are surviving disease-free a fraction of harvested PBSC can result in the administration of relatively low CD34 + cell numbers after each at a median of 494 days (range, 55-1263). No patient died as a direct consequence of low blood cell counts.treatment. The purpose of this analysis was to evaluate the These data demonstrate that PBSC products containing 1.17-2.48 ؋ 10 6 CD34 ؉ cells/kg resulted in relatively engraftment kinetics in 48 patients with malignancy given HDC followed by PBSC containing Ͻ2.5 × 10 6 CD34 + prompt neutrophil recovery in all patients but approximately 10% had delayed platelet recovery. cells/kg. Keywords: engraftment; low CD34 ϩ cells Patients and methodsThe CD34 + cell content of peripheral blood stem cells Patient selection (PBSC) has been shown to be an accurate and proven predictor of engraftment kinetics, especially of platelets, folRecords were reviewed of 2079 nonleukemia patients lowing high-dose chemotherapy (HDC). 1-5 Infusion of treated with HDC and PBSC infusion between March 1991 PBSC containing у5 × 10 6 /k...

Summary:Keywords: high-dose chemotherapy; non-Hodgkin's lymphoma; autologous stem cells The outcomes for patients with non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy (HDC) and peripheral blood stem cell (PBSC) infusion by practicing oncologists in community cancer centersPatients with recurrent or refractory non-Hodgkin's lymin the United States were determined. Eighty-three phoma (NHL) may respond to further conventional treatpatients with NHL, who had failed conventional chemoment but few are cured. 1 It has been known for more than therapy, underwent mobilization of PBSC with chemoa decade that high-dose chemotherapy (HDC) or chemotherapy and a recombinant growth factor in an outradiotherapy followed by autologous stem cell infusion patient facility. At a median of 40 days (range 26-119) results in long-term event-free survival (EFS) in a signifiafter mobilization chemotherapy all received carmuscant fraction of patients with NHL who have failed chemotine (300 mg/m 2 × 1), etoposide (150 mg/m 2 twice a day therapy. 2-6 A large body of data has been accumulated over × 4 days), cytarabine (100 mg/m 2 twice a day × 4 days) the past decade that confirmed these observations. ively. The probabilities of OS and EFS for 27 patientsDespite the curative potential of HDC and autologous in untreated first relapse were 0.52 and 0.44, respectstem cell infusion, many patients with NHL who fail ively, as compared to 0.56 and 0.32, respectively, for 18 chemotherapy in the United States do not have access to patients who had reinduction attempts prior to receivthis therapy because of geographic barriers, high cost assoing mobilization chemotherapy (P = 0.81 for OS and ciated with treatment and the perception that the morbidity 0.99 for EFS). No significant risk factors for the outand mortality of treatment requires referral to a tertiary comes of TRM, relapse/progression, OS or EFS could bone marrow transplant center. 23,24 However, the developbe identified. These data demonstrate that approximent of autologous peripheral blood stem cell (PBSC) mately 40% of patients with NHL who have failed coninfusion has made the delivery of some HDC regimens a ventional chemotherapy become long-term disease-free relatively safe therapeutic procedure allowing clinical trials survivors after mobilization chemotherapy, high-dose to be carried out in community cancer centers by practicing BEAC and PBSC infusion administered in an outpatient oncologists. 6,[25][26][27][28] setting in community cancer centers, with the major The purpose of this analysis was to report the outcome cause of failure being relapse. Results obtained in this of 83 patients with NHL who had failed chemotherapy and study are comparable to published data in similar received HDC with BEAC followed by autologous PBSC patient populations receiving therapy as inpatients, suginfusion in an outpatient private practice setting. gesting that clinical trials involving well-tested HDC regimens can be carried out safely in this setting.

Platelets from two patients with essential thrombocythemia failed to aggregate or release serotonin in response to concentrations of epinephrine that aggregated platelets from normal controls. Therefore, we studied their alpha-adrenergic receptors, using 3H-dihydroergocryptine (3H-DHE), an alpha-adrenergic antagonist. These platelets contained an average (mean +/- S.E.) of 210 +/- 18 and 227 +/- 27 3H-DHE binding sites per platelet--less than half that found on control platelets, 464 +/- 37 (P less than 0.01). In contrast, platelets from two other patients with essential thrombocythemia responded to epinephrine and contained a normal number of 3H-DHE sites. Platelets in essential thrombocythemia demonstrated normal kinetics of 3H-DHE binding and normal affinities for 3H-DHE and for epinephrine. When control platelets were preincubated with a half-saturating concentration of 3H-DHE, there was a diminution of epinephrine-induced platelet function comparable to that seen in essential thrombocythemia. Thus, a deficiency of alpha-adrenergic receptors may account for diminished functional responsiveness of platelets to epinephrine in some patients with essential thrombocythemia.