COPBLAM III: infusional combination chemotherapy for diffuse large-cell lymphoma.

COPBLAM III, a polychemotherapy regimen consisting of cyclophosphamide, infusional vincristine, prednisone, infusional bleomycin, doxorubicin, and procarbazine, was administered to 51 patients with diffuse large-cell lymphoma. Ninety-six percent of patients age 60 or younger achieved a complete response (CR); none have relapsed. Overall, 88% of patients are alive and well and potentially in the survival plateau. For patients greater than 60 years, CR was obtained in 73%, with 42% potentially in the survival plateau, the difference resulting in part from four relapses, three toxic deaths, and one presumed unrelated death. These results in the elderly were paralleled by a relatively reduced ability to tolerate therapy. Toxicity was primarily pulmonary, occurring in 39% of patients, two of whom died. With an overall CR rate of 84%, of which 92% are sustained at a median follow-up of 40 months, COPBLAM III represents a highly effective treatment in a sizeable cohort of patients.

Improved survival duration with combination chemotherapy induction for multiple myeloma: a Southwest Oncology Group Study.

Four hundred forty previously untreated patients with active multiple myeloma were entered into a randomized trial (Southwest Oncology Group [SWOG] study 7927/28) comparing vincristine, melphalan, Cytoxan (Mead Johnson & Company, Evansville, Ind), and prednisone (VMCP) alternating with vincristine, BCNU, Adriamycin (Adria Laboratories, Columbus, Ohio) and prednisone (VBAP) with or without levamisole with vincristine, Cytoxan, and prednisone (VCP) with or without levamisole for induction therapy. The treatment groups were well balanced for all of the known major prognostic factors. Patients receiving VMCP-VBAP responded (greater than or equal to 75% regression) more frequently to induction therapy, both without (54%) and with (44%) levamisole v VCP without (28%) or with (28%) levamisole (P less than .001). In addition, patients receiving VMCP-VBAP (+/- levamisole) had a survival duration determined to be significantly increased by all forms of analysis: 48 and 33 months for VMCP-VBAP without and with levamisole v 29 and 26 months for VCP without and with levamisole (P = .011 overall). Levamisole did not improve response rates or survival duration (P greater than or equal to .1), nor did it prolong remission in the maintenance phase (P = .85). Analysis of SWOG study 7704/05 (updated April 1985) confirmed improved survival for combination therapy v MP, but no benefit for levamisole. The overall findings support the use of VMCP-VBAP as an excellent treatment option for remission induction in patients with active myeloma of all stages and prognostic categories.

Analysis of prognostic factors for the outcome of marrow transplantation or further chemotherapy for patients with acute nonlymphocytic leukemia in first remission.

To test whether variables at diagnosis can identify patients with acute nonlymphoblastic leukemia (ANL) for whom bone marrow transplantation (BMT) is more likely to be of benefit and those for whom continued chemotherapy is a better approach, the association of 15 clinical and laboratory factors with outcome was investigated among 220 patients (ages 1 to 53 years) treated with cyclophosphamide and total body irradiation (TBI) followed by allogeneic BMT, and among 392 patients (ages 13 to 50) administered intensive chemotherapy. In the BMT group, female sex, younger age, the absence of hepatitis during induction, a larger percentage of circulating blasts, and a shorter duration of symptoms were associated with longer survival, whereas only female sex and younger age favorably influenced disease-free survival (DFS). In the chemotherapy group, younger age, lower WBC at diagnosis, a single successful induction course, and the absence of circulating promyelocytes were associated with longer survival, whereas only a lower WBC and a lower percentage of peripheral neutrophils were associated with longer DFS. Estimated regression coefficients for treatment-by-prognostic-factor interactions were used to characterize subgroups of patients in which one treatment or the other produced better outcomes. BMT and chemotherapy produced similar durations of survival in a subset of patients characterized by many or all of the following: older age, male sex, achievement of complete remission (CR) after one induction, and absence of circulating blast cells at presentation. These data suggest that, using pretreatment variables, subgroups of patients can be identified for whom either BMT or continued chemotherapy is most likely to be beneficial.

Unfavorable histologies of non-Hodgkin's lymphoma treated with ProMACE-CytaBOM: a groupwide Southwest Oncology Group study.

Chemotherapy using cyclophosphamide, doxorubicin, etoposide, cytarabine, bleomycin, vincristine, methotrexate with leucovorin, and prednisone (ProMACE-CytoBOM) for patients with intermediate- and high-grade non-Hodgkin's lymphomas was tested by the Southwest Oncology Group (SWOG) to confirm the activity of the regimen and to test the feasibility and safety of administering third-generation drug regimens in a cooperative group setting. On day 1, cyclophosphamide, doxorubicin, and etoposide were administered, followed by cytarabine, bleomycin, vincristine and methotrexate with leucovorin given on day 8. There were 51 complete remissions (CRs) among 78 previously untreated patients (65%) having clinical stage II-IV disease. The median length of follow-up is 37.9 months with 57% of patients alive at 3 years and 50% of CR patients free of disease at 3 years. Patients with diffuse large-cell lymphoma have the best survival (63% at 3 years) and relapse-free survival (RFS; 68% at 3 years with no relapses seen after 14 months). Administration of ProMACE-CytoBOM is feasible and safe in a cooperative group setting with 84% of 537 courses of treatment given exactly according to schedule and fatal toxicities seen in five patients (6%). ProMACE-CytaBOM may represent improved treatment for diffuse large-cell lymphoma, but the modest differences compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) indicate the need for a prospective randomized comparative trial.

Chronic granulocytic leukemia after renal transplantation.

Chronic granulocytic leukemia (CGL) developed in a 31-year-old man after he underwent a third renal transplant. The leukemia was initially controlled with azathioprine sodium and prednisone therapy, but eventually it entered blast cell crisis. This was controlled with an adult acute lymphocytic leukemia protocol with an excellent response. Despite discontinuing treatment with azathioprine and with the use of busulfan to control the peripheral WBC count, the patient maintained stable renal function for one year following treatment of the blast cell crisis and subsequently died of sepsis. We suggest that CGL after renal transplantation is similar to that observed in the general population and can be treated with the usual chemotherapeutic agents for the disorder without sacrificing renal function.

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.

Pregnancy complicated by preeclampsia-eclampsia with the syndrome of hemolysis, elevated liver enzymes, and low platelet count: how rapid is postpartum recovery?

The rapidity of postpartum disease recovery for severe preeclampsia associated with hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome) has not been well studied. Between January 1980 and March 1989, 158 pregnancies with preeclampsia-eclampsia complicated by HELLP syndrome were managed at the University of Mississippi Medical Center. The 70 patients with platelet nadir below 50,000/microL (class 1 HELLP syndrome) required as long as 11 days for all members to achieve a platelet recovery concentration of more than 100,000/microL, whereas all 88 gravidas with platelet nadir between 50,000-100,000/microL (class 2 HELLP syndrome) exceeded this platelet concentration by the sixth postpartum day, a statistically significant difference (P less than .0001). The interval between delivery and the onset of diuresis (mean +/- SD) was significantly longer in class 1 than in class 2 patients with milder disease (22.7 +/- 18.9 compared with 15.9 +/- 11.1 hours). Significantly more postpartum days were required in class 1 than in class 2 HELLP parturients for the lactic dehydrogenase (LDH) concentration to decrease below 500 IU/L (4.2 +/- 4.9 compared with 3.2 +/- 2.7 days). No women in the class 2 group required plasma exchange therapy to effect disease arrest and reversal, but 11 of 58 severely ill women in class 1 were treated with this modality. We conclude that the platelet count and LDH serum concentration, as indicators of HELLP severity and recovery, are clinically useful tools and that a more protracted postpartum recovery period should be expected for progressively severe expressions of HELLP syndrome.

Double heterozygosity for the codon beta 39 C-to-T nonsense mutation and a triplicate alpha-globin gene locus can cause "dominantly" inherited beta-thalassemia intermedia.

BACKGROUND: A beta-thalassemia intermedia phenotype can be caused by multiple genotypes. METHODS: We studied a family where the mother was hematologically normal and both father and daughter had beta-thalassemia intermedia. RESULTS: Both affected individuals were heterozygous for a codon 39 CAG-to-TAG mutation. They also were heterozygous for a triplicate alpha-globin gene locus (alphaalphaalpha(anti 3.7)). CONCLUSIONS: This compound heterozygous condition of a beta39 C-to-T mutation and triplicate alpha-globin gene increases alpha:beta-globin chain imbalance and accounts for the presence of beta-thalassemia intermedia. The proband received both an abnormal beta-globin gene and a triplicate alpha-globin locus from her father. Although the phenotype seems to be dominantly inherited, because of independent segregation of the alpha- and beta-globin genes, it is more accurately an example of polygenic inheritance.

Dye-dilution techniques using aminohippurate sodium: do they accurately reflect amniotic fluid volume?

OBJECTIVE: To determine whether the dye-dilution technique using aminohippurate sodium accurately measures amniotic fluid volume. METHODS: Singleton pregnancies with intact membranes undergoing a Cesarean delivery had their amniotic fluid volume assessed by the dye-dilution technique and direct measurement. RESULTS: Fifteen women were prospectively assessed. Six patients had their amniocentesis on the delivery table and nine patients at 4-24 h prior to the Cesarean delivery. The six women undergoing an amniocentesis just before delivery had good concordance between the dye-determined and direct measurement of amniotic fluid volume (r = 0.99, p = < 0.001). Among the nine women with varying times from amniocentesis to direct measurement, the correlation was not significant (r = 0.36, p = 0.08). The percentage difference between the dye-determined and directly measured amniotic fluid volume was significantly smaller in the women undergoing amniocentesis just prior to delivery (7%) than in the women with varying times from amniocentesis to delivery (37%, P < 0.001). CONCLUSION: Dye-determined amniotic fluid volume accurately reflects actual amniotic fluid volume but the dye-determined concentrations, in vivo, may undergo rapid changes.

Systemic treatment of cancer in the elderly.

The goal of this review is to provide a readable and exhaustive reference in three major areas of geriatric oncology: complications of chemotherapy and radiotherapy, responsiveness of cancer to systemic treatment, social issues in the care of elderly patients with terminal illnesses. The conclusions of this study are: 1. Progressive deterioration of renal function is the most consistent change of aging. Adjustment of doses of renally excreted drugs to individual creatinine clearance may prevent life-threatening myelotoxicity in the elderly. 2. Intensive chemotherapy regimens (acute leukemia, non Hodgkin's lymphoma) cause more serious and prolonged myelotoxicity in the elderly. Elderly are more susceptible than younger patients to cardiotoxicity and central and peripheral neurotoxicity. Age is a poor predictor of complications in other organs or systems. 3. The prognosis of patients with Hodgkin's disease worsens with aging, possibly due to increased prevalence of mixed cellularity histology. It is controversial whether the prognosis of other neoplasias is poorer. Prognosis is not age-related in multiple myeloma. In general, elderly in good performance status may benefit from systemic cancer treatment to the same extent as younger patients, except for Hodgkin's disease. 4. The Informal Support Network, epitomized by the family, appears the most suitable environment to care for the elderly with cancer.

Bone marrow transplantation: a new treatment approach for Mississippians.

Bone marrow transplantation makes it possible to treat patients with malignancies using doses of systemic chemotherapy and/or radiotherapy that otherwise would result in fatal hematologic toxicity. This approach has found its widest application in the treatment of hematologic malignancies, but it is also being used for aplastic anemia, severe immunodeficiency diseases, and selected solid tumors. The University of Mississippi will soon (October, 1991) be able to offer this treatment approach to Mississippians; therefore the indications, the general technique, and results of transplantation for a variety of diseases are reviewed herein.

Utilization of parenteral nutrition in patients receiving peripheral blood stem cell transplantation.

A paucity of information is available on the use of parenteral nutrition (PN) in patients undergoing peripheral blood stem cell transplantation (PBSCT). To characterize the utilization of PN in patients undergoing PBSCT, we conducted a retrospective chart review study on adult patients receiving autologous and allogeneic PBSCT. Data collection included nutritional parameters such as indications for PN, days of PN administration, and PN-associated complications (i.e., metabolic, infectious, and mechanical). Outcome parameters assessed included length of hospitalization, days to engraftment, graft versus host disease (GVHD), and veno-occlusive disease (VOD). A total of twenty-one consecutive patients were evaluated with 12 receiving allogeneic PBSCT and 9 receiving autologous PBSCT. The allogeneic group received PN for a mean of 25 days compared to 21 days for the autologous group. The rate of metabolic abnormalities was significantly higher in the allogeneic group compared to the autologous group (1.02 abnormalities/PN days vs 0.61 abnormalities/PN day, p < 0.05), but mechanical and infectious complications were similar between the two groups. Length of hospitalization, days to engraftment, incidence of GVHD and VOD did not differ significantly between the two groups. However, mortality prior to discharge was significantly higher in the allogeneic vs autologous group (58% vs 0%, p < 0.05). We conclude that allogeneic PBSCT patients appear to be at a greater risk for metabolic complications while receiving PN as compared to autologous PBSCT patients. As nausea and vomiting are two primary reasons for initiation of PN in this patient population, further studies of aggressive antiemetic therapy may prove to decrease the need for PN in PBSCT patients.

Autoimmune thrombocytopenic purpura: current concepts and recommended practices.

Autoimmune thrombocytopenic purpura is the most common autoimmune disorder encountered in the pregnant patient. It is potentially fatal for the mother and fetus yet treatable and potentially curable. Analysis of current perinatal literature reveals not only a great deal of interest and activity in the study of this syndrome and its special problems during pregnancy but also significant controversy. The disease can be acute or chronic and vary in time of onset and severity of manifestations. If not forewarned with an awareness of this disorder's pathogenesis and potential fetal effects particularly in the pregnant woman who has undergone splenectomy, the obstetrician cannot respond appropriately. The usefulness of platelet antibody determinations to facilitate obstetric management decisions is discussed. The importance of cooperative care among the obstetrician, hematologist, and neonatologist is emphasized. Recommendations for management of autoimmune thrombocytopenic purpura in pregnancy are derived from a review of current concepts of the disorder's pathogenesis, pathophysiology, criteria for diagnosis, and modes of therapy as well as special maternal/fetal considerations of antepartum, intrapartum, and postpartum care.

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.

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.

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.

Focal glomerulosclerosis in Hodgkin's disease necessitating peritoneal dialysis.

A 16-year-old white boy had nephrotic syndrome due to focal segmental glomerulosclerosis six months before the diagnosis of Hodgkin's disease was established. Peritoneal dialysis was necessary for volume control after one month of unsuccessful therapy with high doses of corticosteroids. Nephrosis remitted after two courses of chemotherapy.

The intrapartum platelet count in patients with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome: is it predictive of later hemorrhagic complications?

OBJECTIVE: We wished to determine in patients with HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) whether (1) there is an intrapartum threshold platelet count that is predictive of immediate or delayed hemorrhagic complications and (2) whether prophylactic platelet transfusion at delivery prevents these outcomes. STUDY DESIGN: In this retrospective, descriptive study, the peripartal courses of 132 patients with class 1 (< or = 50,000/microliters platelet nadir) and 160 patients with class 2 (> 50,000 but < or = 100,000/microliters platelet nadir) HELLP syndrome were reviewed with special attention to laboratory data, evidence of hemorrhage, and details of platelet transfusion therapy. RESULTS: A higher incidence of postpartum hemorrhagic complications (p < 0.001) occurred in class 1 versus class 2 HELLP pregnancies. The tendency to have postpartum incisional bleeding after abdominal or vaginal delivery was related to the degree of thrombocytopenia (p = 0.006). The antepartum threshold platelet count most predictive of subsequent postpartum hemorrhagic complications was < or = 40,000/microliters. The prophylactic administration of platelets does not appear to have either significantly decreased the incidence of postpartum hemorrhagic complications or significantly hastened normalization of the postpartum platelet count. CONCLUSIONS: Although bleeding in the gravid patient is related to more factors than platelet count alone, patients with HELLP syndrome in whom an intrapartum platelet count above 40,000/microliters maintained are unlikely to have clinically significant postpartum bleeding. Patients with intrapartum platelet counts < or = 40,000/microliters, however, are at significant risk for postpartum bleeding, but prophylactic platelet transfusion at delivery does not ensure a significantly lower incidence of postpartum hemorrhagic complications.