Thrombotic thrombocytopenic purpura: evolution across 15 years.

Thrombotic thrombocytopenic purpura (TTP) was originally described 70 years ago. It is considered an uncommon disorder with a reported occurrence rate of one case per 1 million patients. Mortality has decreased from almost 100% early on to 30-50% with the advent of newer treatment methods. We reviewed 41 patients with a diagnosis of TTP spanning the years 1980 to mid 1994. We found a much higher case rate, one per 6000 hospital admissions, and an overall death rate of 40%. However, isolating 5 year periods we noted a marked fall in mortality from 54% (1980-1984), 44% (1985-1989), to 18% (1990-1994). Previous reports describe relapsing TTP and report an incidence of 7-15% although very recent data suggests a higher incidence. In our study, we found an overall relapse rate of 25% and by 5 year periods 23% (1980-1984), 13% (1985-1989), and 46% (1990-1994). We suggest that the improvement in survival and the increase in relapse rate are related and reflect more effective therapy for this once almost always fatal disease. Patients now survive their initial episode and thus are at risk for recurrence. Identification of risk factors for relapse will require further study.

Effect of blood transfusion in patients with gynecologic malignancy.

OBJECTIVES: To determine the effect of blood transfusion on long-term outcome (disease-free interval, recurrence of disease after treatment, and survival) in women with invasive gynecologic malignancy. METHODS: In this retrospective study, 125 patients with gynecologic malignancy were assessed over a 36-month period. The variable of whether patients received blood transfusion during therapy was used to divide the sample into two groups. RESULTS: There were no differences in the age, ethnicity, and site-stage of tumor of the two groups. Treatments (surgery, radiotherapy, chemotherapy, or multimodal) were similar between the two groups, as were initial hematocrits. The disease-free interval was significantly better in women who did not receive homologous blood (P < 0.001). Life table analysis illustrated that more patients were alive and free of disease if they did not receive blood (P < 0.001). Likewise, persistence-recurrence of cancer was more common in the transfusion group (P < 0.001). Finally, overall survival time was adversely affected by transfusion (P = 0.045). CONCLUSIONS: The use of blood products in patients with invasive gynecologic cancer is associated with enhanced recurrence or persistence of malignancy, a decrease in the disease-free interval, and reduction in the probability of survival without evidence of disease.

Low-dose involved field radiation after chemotherapy in advanced Hodgkin disease. A Southwest Oncology Group randomized study.

OBJECTIVE: To determine if low-dose involved field radiation after complete remission induction with chemotherapy is effective in preventing relapse and improving survival in patients with stage III or IV Hodgkin disease. DESIGN: A randomized controlled trial with a median follow-up time of 8.1 years. SETTING: A Southwest Oncology Group multi-institutional study. Patients were entered from university- and community-based practices. PATIENTS: 278 adults with clinical or pathologic stage III or IV Hodgkin disease, who achieved complete responses after 6 cycles of MOP-BAP (nitrogen mustard, vincristine, prednisone, bleomycin, doxorubicin, and procarbazine) and who agreed to be randomly assigned to either radiation or no further treatment. INTERVENTION: Patients were assigned to either no further treatment or low-dose radiation to all initially involved sites (radiation dose, 2000 cGy to lymph node areas and 1000 to 1500 cGy to other involved organ sites). MEASUREMENTS: Differences in remission duration, relapse-free survival, and survival. RESULTS: Remission duration, relapse-free survival, and overall survival were similar for the two groups (P = 0.09, P > 0.2, and P = 0.14, respectively). Factors that predicted shorter remission duration in a multivariate analysis were nodular sclerosis histology, bulky disease, and receipt of less than 85% of planned chemotherapy. Low-dose radiation improved remission duration in the subgroups of patients with nodular sclerosis and bulky disease. For the 169 patients with nodular sclerosis, the 5-year remission-duration estimate was 82% for the low-dose radiation group and 60% for the no further treatment group (P = 0.002). For all patients with bulky disease, the 5-year remission-duration estimate was 75% for the low-dose radiation group and 57% for the no further treatment group (P = 0.05). No difference in overall survival was noted between low-dose radiation and no further treatment in all patients or major subgroups. The 5-year survival was 86% for all patients who had a complete response as well as for patients in the nodular sclerosis subgroup. CONCLUSIONS: Low-dose involved field radiation after MOP-BAP chemotherapy in patients with stage III or IV Hodgkin disease did not prolong remission duration or overall survival in randomized patients. However, remission duration was prolonged in several subgroups of patients, most prominently in those with nodular sclerosis histology.

The effect of provider education on blood utilization practices.

OBJECTIVE: Our aim was to determine prospectively if a process of provider education and subsequent audit of transfusion criteria can reduce inappropriate blood product infusion. STUDY DESIGN: Beginning in December 1990, a year-long process of provider education and quality assurance audit, with the use of guidelines based on National Institutes of Health blood product consensus conferences, was instituted. After this orientation and education period, the medical records were reviewed for patients on the obstetrics and gynecology service from Dec. 1, 1990, through Sept. 30, 1991, who received blood products (packed red blood cells, fresh-frozen plasma, cryoprecipitate). This group was compared with patients cared for by our service over a similar period before the institution of these guidelines. The incidence of cesarean birth and operative intervention for gynecologic malignancies, as well as the number of major operative gynecologic procedures, was found to be unchanged during the total study period (Dec. 1, 1988, through Sept. 30, 1991). RESULTS: In 1989 there were 1236 units of blood products transfused; in contrast, in 1991 428 units of blood were transfused. In 1989, 107.9 +/- 59.9 units of packed cells per month were used in 33.6 +/- 16.8 patients (3.2 units per patient). In contrast, in 1991, 14.4 +/- 5.8 patients per month received transfusions (2.82 units per patient) with 40.7 +/- 17.2 units of packed cells (p < 0.0001). This represents a 75% decrease in the total number of packed cells and a 60% decrease in the number of patients undergoing transfusion per month. Similar reductions in the usage of cryoprecipitate and fresh-frozen plasma were noted (p = 0.024 and 0.002, respectively). Acute operative blood loss was the most common indication for transfusion. Abdominal hysterectomy was the most common procedure followed by exploratory laparotomy and cesarean section. No patients in whom blood was not used had untoward effects. CONCLUSION: Education as to appropriate blood utilization and concurrent quality assurance audit techniques can safely reduce blood usage on a busy obstetrics and gynecology service in a tertiary care center.

The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study.

One hundred and forty one patients were treated in a combined Eastern Cooperative Oncology Group and Southwest Oncology Group phase-III study evaluating low-dose cytarabine (LDAC) versus supportive therapy for the treatment of myelodysplastic syndrome (MDS). Patients were randomized to either cytarabine 10 mg/m2 subcutaneously BID or supportive therapy. Central pathology review was required. All patients were classified according to the FAB criteria for MDS. The overall concordance rate for the MDS subtype was 52%, and 25 patients were pathology exclusions, including 20 with AML. The overall response rate to a single cycle of LDAC was 32%, with 11% complete and 21% partial responses. The median duration of response was 5.9 months, with a range of 1.4-33.5 months. Responses were seen in all subtypes. Infections were more common in the LDAC arm. There was no difference in the time to progression or the overall survival for patients treated with LDAC or supportive therapy. The incidence of leukemic transformation was similar in both arms at 15%, but it differed according to the MDS subtype. Patients receiving LDAC had a decreased transfusion requirement after 3 months. There was a significant correlation between the degree of cytoreduction after receiving a single cycle of LDAC and survival. This survival difference was most marked in patients with the RAEB and RAEB-T subtypes. Although LDAC produced responses in all subtypes of the MDS, there was no effect on overall survival or transformation to AML. However, selected patients benefited from a single cycle of LDAC with durable responses. A cytoreductive effect appears to be required for a durable response. Future studies should include pathology review and must address the clinical and biological heterogeneity of MDS.

Late intensification with POMP chemotherapy prolongs survival in acute myelogenous leukemia--results of a Southwest Oncology Group study of rubidazone versus adriamycin for remission induction, prophylactic intrathecal therapy, late intensification, and levamisole maintenance.

Between August 1978 and September 1982, 642 patients with newly diagnosed acute myelogenous leukemia (AML) were entered onto a Southwest Oncology Group Study which addressed four questions. (i) What is the comparative utility of rubidazone versus adriamycin in remission induction? (ii) What is the role of prophylactic intrathecal therapy in AML? (iii) Does late intensification affect treatment outcome? (iv) Does maintenance with levamisole affect disease-free survival or overall survival? Among 611 evaluable patients, 329 (54%) achieved complete remission. There was no difference in the remission rate between those patients receiving rubidazone (54%) and those receiving adriamycin (54%) as part of the induction regimen. Prophylactic intrathecal therapy with cytosine arabinoside had no effect on the incidence of central nervous system disease or survival. After nine months of complete remission, patients were randomized between late intensification with POMP (mercaptopurine + vincristine + methotrexate + prednisone) or continued maintenance with OAP (vincristine + cytosine arabinoside + prednisone). T patients randomized to late intensification had better survival and disease-free survival, compared to those randomized to receive no late intensification (p = 0.027 and 0.030, respectively). At twelve months of remission, surviving patients were randomized to receive levamisole or no further treatment. There was no evidence that levamisole affected survival or disease-free survival.

Use of continuous flow erythrocytapheresis in pregnant patients with sickle cell disease.

The role of partial prophylactic red cell exchange transfusion in the management of pregnant patients with major sickle hemoglobinopathies is unclear. Over a 10-year period, 131 pregnant patients with major hemoglobinopathies (HbS 101, HbS-C 30) were managed by the same group of physicians. Of these, 103 received partial prophylactic exchange transfusion early during prenatal care while 28 received blood only when serious complications developed (control group). Patients treated with exchange transfusion received continuous flow erythrocytapheresis on an outpatient basis. The results indicate that there were fewer crises (P = .0001), a reduction in other significant medical complications (P = .002), and a decrease in maternal hospital days (P = .05) in those receiving prophylactic transfusions compared to women in the control group. The number of preterm deliveries (P = .004), the prevalence of low birthweight infants (P = .01), and the perinatal death rate (P = .01) were significantly lower among those who were routinely transfused. Two patients developed hepatitis, five had transfusion reactions, and 11 were found to have alloantibodies among those receiving prophylactic transfusions versus one, two, and five patients, respectively, in the control group. The results indicate a benefit of this methodology in the treatment of pregnant sickle cell patients in our population. However, a national collaborative randomized study is needed to adequately address the controversy regarding the use of red cell exchange in the pregnant sickler.

Pathogenetic implications of internuclear bridging in myelodysplastic syndrome. An Eastern Cooperative Oncology Group/Southwest Oncology Group Cooperative Study.

Numerous morphologic features have been described in bone marrow and peripheral blood in myelodysplastic syndrome (MDS). We draw attention to a high incidence of a subtle morphologic feature, internuclear bridging (INB), not previously recognized as a morphologic feature in MDS. The occurrence of INB in MDS suggests an underlying abnormality of mitotic division that could explain the impaired production of hematopoietic cells, the addition and deletion cytogenetic changes, and the stepwise disease progression and cytogenetic progression characteristic of MDS. Lack of awareness that INB occurs in MDS may cause confusion of MDS and congenital dyserythropoietic anemia type I, a congenital process also characterized by INB.

Transient acquired factor X deficiency: report of the use of activated clotting concentrate to control a life-threatening hemorrhage.

Acquired deficiency of factor X is an uncommon occurrence. It has usually developed in association with amyloidosis [8] and, in that setting, it has been irreversible. Transient deficiency appears to be associated with an acute respiratory infection in the majority of cases. Bleeding in these patients can be life-threatening and has been difficult to control. Konyne produces a brief correction of the prothrombin time and an elevation in the factor X level, but has not been effective in stopping bleeding. We report the first successful correction of prothrombin time and clinical resolution of bleeding attending the use of Autoplex T. If bleeding persists after appropriate specific factor replacement and the clinical condition warrants, the use of Autoplex T (activated prothrombin complex) deserves prompt consideration.

Thrombotic thrombocytopenic purpura and pancreatitis.

Abdominal pain is frequently encountered in patients with thrombotic thrombocytopenic purpura (TTP). Often the pain is secondary to inflammation of the pancreas. A case is presented in which the usual signs of TTP developed well after the clinical and laboratory demonstration of pancreatitis, raising the possibility that the pancreatic inflammation triggered the onset of TTP. Treatment with plasmapheresis resulted in prompt improvement. TTP should be considered in patients with abdominal pain or pancreatitis in whom thrombocytopenia, microangiopathic hemolytic anemia, neurologic changes, fever, and renal disease are present.

Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone alone or with levamisole or with levamisole plus BCG for malignant lymphoma: a Southwest Oncology Group Study.

Between 1977 and 1983 the Southwest Oncology Group (SWOG) evaluated chemotherapy alone (cyclophosphamide, doxorubicin, vincristine, prednisone; CHOP) or chemoimmunotherapy (CHOP-levamisole or CHOP-levamisole-BCG) in a randomized prospective clinical trial involving 715 eligible patients with all types of malignant lymphoma (ML). Of 281 evaluable patients with favorable histologic types of ML, 171 (61%) achieved complete remission (CR) and there was no difference in CR rate, CR duration, or survival according to the type of initial treatment. Of 388 evaluable patients with unfavorable histologic types of ML, 194 (50%) achieved CR. Levamisole appeared to adversely affect CR rates in nodular mixed and nodular large-cell lymphoma and CR duration in patients with unfavorable histology ML. Chemoimmunotherapy with levamisole or levamisole-BCG offers no advantage in terms of CR rates, CR duration, or survival compared to CHOP chemotherapy alone, and levamisole may have had an adverse impact on outcome in certain subtypes of ML.

Institutional performance in application of the FAB classification of acute leukemia. The Southwest Oncology Group experience.

Institutional performance in application of the French-American-British (FAB) classification of acute leukemia in The Southwest Oncology Group is presented, demonstrating a disparity between institutional and expert performance. A significant improvement is shown with an educational effort coupled with experience in use of the classification, and the importance of cytochemistry in the use of the classification is illustrated. A simplification of the classification, merging M1, M2, and M4 as M7, is proposed. This simplification improves institutional performance in use of the classification, while preserving distinctions that appear clinically important.

Reproducibility of the French-American-British classification of acute leukemia: the Southwest Oncology Group Experience.

After initial French-American-British (FAB) diagnosis by a multiinstitutional Southwest Oncology Group panel, slides of acute leukemia cases were recirculated to panel members for second review. The reproducibility of the FAB classification is analyzed. The classification is reproducible in the 70% range in panel reviewer hands and allows remarkable reproducibility in the morphologic and cytochemical distinction of acute lymphoid leukemia (ALL) from acute myeloid leukemia (AML). The limitations of a morphologic and cytochemical classification of acute leukemia are discussed. A simplification of the FAB system, merging M1, M2, and M4 as M7, is proposed; this simplification improves the system's reproducibility.

Race, age, and pernicious anemia.

We have described a 22-year-old black man with pernicious anemia, classically considered a disease of middle-aged and elderly Northern Europeans. It is considered rare in non-caucasians and children. The majority of very young patients have been considered to have the congenital form of pernicious and anemia, characterized by absence of intrinsic factor with normal gastric mucosa and acid production. We have seen no patients with this type of the disease. Furthermore, all five patients under 25 years of age and eight of nine under 35 were black. We found no racial difference in the incidence of pernicious anemia, but we believe it may occur at a younger age in black patients.

Response of chronic myelogenous leukemia patients to COAP-splenectomy. A Southwest Oncology Group study.

Eighty-seven patients from 18 institutions with a confirmed diagnosis of chronic myelogenous leukemia were registered on a Southwest Oncology Group protocol for multiagent induction and single-agent maintenance chemotherapy, with randomization to an immunotherapy arm. Elective surgical splenectomy was performed for 42 patients at the completion of 3 months of induction therapy. Final analysis of the study revealed statistically significant survival advantages were correlated with age, splenectomy, the absence of hepatic leukemic infiltrate at the time of splenectomy, and race.

Mitoxantrone in refractory nonHodgkin's lymphoma. A Southwest Oncology Group study.

A phase II study of mitoxantrone in nonHodgkin's lymphoma was conducted by the Southwest Oncology Group between July 1981 and May 1982. The study involved 37 patients with histologically proven nonHodgkin's lymphoma, who were not eligible for higher priority protocols but had clearly measurable disease. Patients received mitoxantrone, 12 mg/m2 at intervals of 3 weeks, with a 10% increase in dose in the absence of myelosuppression and a 17% reduction for a WBC of less than 2 X 10(9) cells/L or a platelet count of less than 50 X 10(9)/L. The median number of previous regimens was three. Doxorubicin, in a median dose of 242 mg/m2 (range 12 to 650 mg/m2) had been previously given to 34 of the 37 patients. The Pathology Panel for Lymphoma Clinical Studies reviewed 31 (84%) of the lymphomas. Four of the ten follicular, small cleaved cell lymphomas responded compared with one of nine diffuse, large cell lymphomas. The median duration of response was 231 days. A median of two doses of mitoxantrone (range 1 to 18) was given. The median WBC nadir was 5.1 X 10(9)/L (range 04. to 9.4 X 10(9)/L), and the median lowest WBC for all doses was 2.4 X 10(9)/L (range 0.4 to 16 X 10(9)/L). Among 17 patients with a first WBC nadir of less than 3 X 10(9)/L, there were three partial responses compared with four responses (one complete, three partial) from nine patients with a WBC over 3 X 10(9)/L. There were seven responses (one complete, six partial) among 23 patients who had received up to three previous regimens, whereas only two of 14 patients receiving more than three previous regimens responded (one complete, one partial response). The response rate was independent of the previous dose of doxorubicin with five responses out of 23 patients who received a total dose of less than 300 mg/m2 and four responses out of 14 patients who received greater than 300 mg/m2. These data are compatible with the hypothesis that mitoxantrone alone is active against previously treated low-grade lymphomas and that the response rate is independent of the total dose of prior doxorubicin received and the degree of myelosuppression. Mitoxantrone may not be cross resistant with doxorubicin.