The dose of infused lymphocytes in the autograft directly correlates with clinical outcome after autologous peripheral blood hematopoietic stem cell transplantation in multiple myeloma.

Absolute lymphocyte count at day 15 (ALC-15) after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT) is an independent prognostic factor for survival in multiple myeloma (MM); however, factors affecting ALC-15 in MM remain unknown. We hypothesized that the dose of infused peripheral blood autograft lymphocytes (autograft absolute lymphocyte count: A-ALC) impacts ALC-15 recovery. Between 1989 and 2001, 267 consecutive MM patients underwent APHSCT. We set out to determine the correlation between A-ALC and ALC-15 and the utility of A-ALC as a marker for ALC-15 recovery. A-ALC was found to be both a strong predictor for area under curve (AUC=0.93; P=0.0001) and strongly correlated with (r(s)=0.83; P=0.0001) ALC-15 recovery. Higher infused A-ALC was significantly correlated with an ALC-15>/=500/microl. In addition, median post-transplant overall survival (OS) and time to progression (TTP) were longer in patients who received an A-ALC>/=0.5 x 10(9) lymphocytes/kg versus A-ALC <0.5 x 10(9) lymphocytes/kg (58 vs 30 months, P=0.00022; 22 vs 15 months, P<0.00012, respectively). Multivariate analysis demonstrated A-ALC as an independent prognostic indicator for OS and TTP. These results indicate that an infused dose of autograft lymphocytes significantly impacts clinical outcome post-APHSCT in MM.

Treatment of renal failure associated with multiple myeloma. Plasmapheresis, hemodialysis, and chemotherapy.

The aims of this study were to examine in a prospective, randomized trial the efficacy of plasmapheresis in preventing irreversible renal failure in patients with multiple myeloma and to study the renal biopsy tissues from such patients. Twenty-one patients with active myeloma and progressive renal failure were randomized to one of two groups: group 1, forced diuresis and chemotherapy (10 patients), and group 2, forced diuresis, chemotherapy, and plasmapheresis (11 patients). Plasmapheresis and chemotherapy lowered the serum myeloma protein value much more rapidly than chemotherapy alone. Of 5 patients who were oliguric and undergoing dialysis at presentation, only 3 who were treated by plasmapheresis recovered. Of 16 polyuric patients, 5 in group 1 and 7 in group 2 showed improvement in renal function. The main factor that determined irreversibility of renal failure was the severity of myeloma cast formation.

Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelination.

We present six patients with acute fulminant episodes of CNS inflammatory demyelination who responded to therapeutic plasmapheresis after failing a course of high-dose methylprednisolone administered IV. Neurologic improvement occurred in three of the patients following the second plasmapheresis. Dramatic improvement in motor function (four patients) and language (two patients) began within 2 to 14 days and persisted during the 6 to 35 months (mean, 15 months) of follow-up. Results of this uncontrolled study suggest that plasmapheresis in the absence of other immunosuppressive drugs may have a role in the treatment of severe episodes of inflammatory demyelination in a select subset of MS patients.

Plasma exchange for severe attacks of CNS demyelination: predictors of response.

The authors reviewed 59 consecutive patients treated with plasma exchange (PE) for acute, severe attacks of CNS demyelination at Mayo Clinic from January 1984 through June 2000. Most patients had relapsing-remitting MS (n = 22, 37.3%), neuromyelitis optica (NMO) (n = 10, 16.9%), and acute disseminated encephalomyelitis (n = 10, 16.9%). PE was followed by moderate or marked functional improvement in 44.1% of treated patients. Male sex (p = 0.021), preserved reflexes (p = 0.019), and early initiation of treatment (p = 0.009) were associated with moderate or marked improvement. Successfully treated patients improved rapidly following PE, and improvement was sustained.

Mixed lymphocyte culture, phytohemagglutinin stimulation, and matching grade: clinical relevance in renal transplantation from living related donors.

Mixed lymphocyte cultures (MLC), including phytohemagglutinin (PHA) stimulation and HLA-A and HLA-B loci typing of donor and recipient, were performed on 70 renal allograft recipients and relevant family members. Graft survival was correlated retrospectively with matchnd PHA response index (PHARI), in order to assess the clinical relevance of each variable singly or jointly. Overall graft survival was significantly associated with SI (log10) (P less than 0.001) and matching grade (P = 0.027). No significant association with either PHARI or II was detected (P greater than 0.10). In addition, the product of the last two indices--the lymphocyte response index (LRI)--was not found to be related to graft survival (P greater than 0.10). Survival of grafts with one-haplotype identity was significantly associated with SI (P = 0.002). Survival in this group was not found to be related to II, PHARI, or LRI, considered either alone or jointly (P greater than 0.10). Grafts with two-allele-identical grafts, whereas PHARI did not differ. SI and matching grade were related significantly to graft survival and appeared to be the most important variables.

Low-density lipoprotein apheresis for the treatment of refractory hyperlipidemia.

The advent of treatment with 3-hydroxy-3-methylglutaryl coenzyme A inhibitors has meant that, with a combination of diet and drug therapy, adequate control of serum cholesterol concentrations can be achieved in most patients with hypercholesterolemia. However, some patients, primarily those with familial hypercholesterolemia (FH), may require additional therapy to lower their cholesterol levels. In recent years, low-density lipoprotein (LDL) apheresis has emerged as an effective method of treatment in these patients. The criteria for commencement of LDL apheresis are LDL cholesterol levels of 500 mg/dL or higher for homozygous FH patients, 300 mg/dL or higher for heterozygous FH patients in whom medical therapy has failed, and 200 mg/dL or higher for heterozygous FH patients with documented coronary disease and in whom medical therapy has failed. In addition to cholesterol lowering in patients with FH, other indications for LDL apheresis are emerging. These include its use in the treatment of graft vascular disease in patients receiving cardiac transplants as well as in the treatment of certain glomerulonephritides. This review examines the role of LDL apheresis in the management of lipid disorders and the evidence available to support its use in clinical practice.

Hemolytic transfusion reaction. Recent experience in a large blood bank.

Data on 47 cases of hemolytic transfusion reactions are presented along with a review of the literature. Human error and limitations of current techniques of compatibility testing remain the major causative factors of hemolytic transfusion reactions.

Removal of plasma lipoproteins from circulating blood with a heparin-agarose column.

A method is described for the removal of cholesterol fractions by means of intermittent extracorporeal plasma circulation through a column containing heparin-treated agarose in the presence of calcium. The system allows plasma perfusion in one column while simultaneously recharging another. In vitro testing demonstrated its efficiency, and in vivo testing of a normal dog proved its feasibility. In vitro testing revealed a mean removal of 22% of low-density and very low-density lipoproteins combined. Animal testing did not produce any abnormalities in clinically significant parameters.

Plasmaperfusion and studies of copper metabolism in benign recurrent cholestasis: novel procedures in a rare syndrome.

A 21-year-old woman with recurrent epidsodes of pruritus and jaundice since childhood was diagnosed as having benign recurrent cholestasis, a rare and poorly understood disease. Plasmaperfusion was successfully employed for therapy of the severe pruritus, and various studies of copper metabolism were performed in an attempt to clarify the pathophysiology of this obscure syndrome.

Blood transfusion for the patient who is difficult to transfuse.

There are two types of patients who are difficult to transfuse because of the presence of red cell antibodies, those patients who have an antibody reactive against an antigen of high incidence and those who have multiple antibodies. Possible sources of blood for the patient who has an antibody reactive against a high-incidence red cell antigen include the patient's family, rare donors lacking the high-incidence antigen, and self-donation. Possible sources of blood for those who have multiple antibodies are limited to rare donors lacking the appropriate combination of antigens or to self-donation.

Autologous blood transfusion.

Autologous blood transfusion is a procedure in which blood is removed from a donor and returned to his circulation at some later time. Autologous transfusion can be performed in three ways: (1) preoperative blood collection, storage, and retransfusion during surgery; (2) immediate preoperative phlebotomy with subsequent artificial hemodilution and later return of the phlebotomized blood; and (3) intraoperative blood salvage and retransfusion. All three methods of autologous transfusion offer a potentially superior method of blood transfusion which eliminates many of the problems and complications associated with the banking and administration of homologous donor blood.

Clinical evaluation of a 51Cr-labeled red blood cell survival test for in vivo blood compatibility testing.

Modified red blood cell survival studies with use of 51Cr were performed in three groups of subjects. Group 1 consisted of normal subjects who were given labeled autologous blood, group 2 were subjects in need of blood transfusions and given labeled ABO and Rh crossmatch-compatible blood, and group 3 were patients in need of blood transfusion but in whom problems arose in finding compatible blood. The results of the studies suggest that for patients with blood compatibility problems, normal red blood cell survival values at 1 hour do not exclude the possibility of severe hemolysis 24 hours later. Thus, if a 1-hour test result is normal, the procedure should be extended routinely to 24 hours. Moreover, the test can be used to evaluate the clinical importance of antibodies. We showed that anti-Yka and anti-Lan were clinically significant, but high-titer, low-avidity antibodies, anti-Kna, anti-I, and anti-HI were clinically insignificant in the cases studied. This finding emphasizes the importance of an in vivo test for the final compatibility evaluation in complicated blood replacement problems.

Plasmaperfusion for the treatment of intractable pruritus of cholestasis.

A patient with primary biliary cirrhosis and intractable pruritus was treated with plasmaperfusion of charcoal-coated glass beads on two occasions. The procedures were well tolerated and resulted in the removal of about 70% (494 mumol) of the estimated chenic acid pool. There was, in addition, pronounced amelioration of the pruritus which enabled the patient to sleep through the night without awakening because of itching. The pruritus, however, did not disappear and gradually returned to its preperfusion intensity by the end of the third week after perfusion.

Role of plasmapheresis in thrombocytopenic purpura associated with Waldenström's macroglobulinemia.

A 67-year-old man with Waldenström's macroglobulinemia had a relapse of chronic idiopathic thrombocytopenic purpura (ITP), which had been refractory to corticosteroids, splenectomy, vinca alkaloids, and high-dose intravenous gamma-globulin therapy. A biclonal gammopathy (IgM kappa and IgG lambda) was detected in his serum and was likely responsible for his refractory thrombocytopenia. He was treated with chlorambucil and prednisone. Plasmapheresis was effective in temporarily maintaining platelet counts and in decreasing morbidity until immunosuppression was completely effective against the production of the monoclonal protein. The previously reported experiences with use of plasmapheresis in patients with chronic ITP are discussed. Plasmapheresis may be of value in the treatment of selected patients with severe ITP and monoclonal gammopathy.

Chronic granulomatous disease and the Mcleod phenotype. Successful treatment of infection with granulocyte transfusions resulting in subsequent hemolytic transfusion reaction.

A young man with X-linked chronic granulomatous disease of childhood, who is of the rare McLeod phenotype with antibodies in his serum shown to be hemolytic and reactive against all red cells with normal expressions of the Kell antigens, developed a severe Nocardia pneumonia with abscess formation and was subsequently treated successfully with granulocyte transfusions in spite of the presence of anti-KX in the patient's serum. The anti-KX did not appear to alter significantly the effectiveness of the transfused granulocytes; it did, however, cause a mild hemolytic transfusion reaction. The patient made a remarkable recovery from this episode and his condition has progressed to a state satisfactory enough for him to donate his own blood for storage and possible use in the future.

Infusion flow rates of whole blood and AS-1-preserved erythrocytes: a comparison.

We compared the flow rates of whole blood and erythrocytes resuspended in a new preservative solution (AS-1, consisting of adenine, dextrose, mannitol, and saline) which results in an erythrocyte preparation with a hematocrit lower than that of packed erythrocytes. When 100 ml of AS-1 solution is added to erythrocytes, a hematocrit of 59 +/- 5% is consistently obtained, and the resultant product has an improved flow rate. When we compared the infusion flow rates of whole blood and AS-1-preserved erythrocytes in vitro and in vivo, we found that flow times were shorter for AS-1 erythrocytes than for whole blood in vitro and in vivo, the flow rates of AS-1 erythrocytes and whole blood when expressed per volume were similar in vivo, and the flow rate of AS-1 erythrocytes for erythrocyte mass delivery in vivo was superior to that of whole blood. Thus, we conclude that the flow rates of the two products are comparable.

Use of combined plasmapheresis and immunosuppression in the treatment of Goodpasture's syndrome.

Five consecutive patients with well-documented Goodpasture's syndrome were treated with plasmapheresis and immunosuppression. In all patients, the antiglomerular basement-membrane antibody titers decreased with treatment. In three patients, hemoptysis responded promptly to plasmapheresis. Two patients presenting with severe renal failure required chronic dialysis, and three patients who had serum creatinine levels less than 2.1 mg/dl before treatment improved or had stabilization of their renal function. We confirm that the use of plasmapheresis and immunosuppression is a promising method of treatment in some patients with Goodpasture's syndrome.

A blood bank consultation service: principles and practice.

In the blood bank setting, a close relationship with both clinicians and patients is essential for good medical practice. In July 1982, the Mayo Clinic Blood Bank and Transfusion Services formally organized a consultation service with daily visits to patients of mutual interest to blood bank consultants and clinicians for practice and education. Detailed diaries of this activity were maintained for 12 months, during which time 802 impatient visits were recorded. The most frequent reasons for consultations were clarification or amplification of the clinical history (34.0%), evaluation of transfusion reactions (27.2%), and assessment of serologic problems (18.2%). These consultations resulted in diagnostic, management, and therapeutic recommendations for a wide variety of medical problems. Of the 802 consultations, 23% were conducted at the direct request of clinicians. We believe that a blood bank consultation service is feasible, is enlightening for the blood bank and clinicians, and contributes to patient care.

Erythrocyte morphology in genetic defects of the Rh and Kell blood group systems.

Absence of KX antigen and of normal expression of the Kell system antigens is associated with bizarre red blood cell morphology when observed by either light or scanning electron microscopy. Numerous acanthocytes and dacryocytes have been observed in the peripheral blood smear of an apparently healthy individual with McLeod-phenotype blood, in a male patient with type II chronic granulomatous disease who had a shortened 51Cr red blood cell survival time, and in a minor population of the red blood cells of his carrier mother.

Monoclonal plasma cells in the blood stem cell harvest from patients with multiple myeloma are associated with shortened relapse-free survival after transplantation.

We sought to determine whether circulating tumor cells in the blood stem cell harvest from patients with multiple myeloma are associated with a shortened disease-free survival. Prospective analysis was performed in 33 patients of blood obtained at leukapheresis for future transplantation. An immunofluorescence microscopy procedure identified the tumor cells by their morphology and monotypic light chain staining. Eighteen patients had increased (> or = 0.2 x 10(6)/l) monoclonal plasma cells circulating in the blood at stem cell harvest. Fifteen of the 18 have relapsed, with a median relapse-free survival of 6.2 months. Of 15 patients with < 0.2 x 10(6) cells/l, seven have relapsed, with a median relapse-free survival of 22.5 months (P = 0.008). Patients with circulating plasma cells showed a trend toward shorter overall survival (P = 0.078). In a multivariate analysis using the bone marrow plasma cell labeling index and beta 2-microglobulin, the absolute number of plasma cells in the stem cell harvest achieved borderline significance for predicting relapse-free survival (P = 0.057). In conclusion, increased monoclonal plasma cells in the blood stem cell harvest are associated with a shortened relapse-free survival. This does not necessarily indicate that the circulating plasma cells were responsible for relapse. These results, however, have implications with regard to the timing of obtaining blood stem cells for patients who are candidates for ablative chemotherapy.