Early outcomes after allogeneic stem cell transplantation for leukemia and myelodysplasia without protective isolation: a 10-year experience.

Although it is common practice to use some form of isolation to protect allogeneic stem cell transplant patients from infection, the necessity for these practices in all environments has not been demonstrated. The current study evaluated patterns of infection and 100-day transplant-related mortality in 288 patients with myelodysplasia and leukemia transplanted without isolation. Patients were allowed out of hospital at any time within constraints of the medication schedule. Fever, foci of infection, and positive cultures within 28 days and death within 100 days because of the transplant procedure were recorded. Fever occurred in 57% of patients, and 10% had a clinical or radiographic focus of infection. Most infections were apparently endogenous; blood cultures from 24% of recipients grew organisms, 87% of which were gram-positive bacteria. Four patients (1%) died with aspergillus infection in circumstances indicating that isolation would not have been helpful. Twenty percent of patients remained without evidence of infection throughout. Transplant-related mortality at 100 days was 1% for 108 patients with early leukemia receiving transplants from matched siblings. For patients at higher risk, by virtue of donor and/or disease status, mortality was 21%. These figures compare favorably with those reported to the International Bone Marrow Transplant Registry, the majority of patients having been subjected to some form of isolation. We conclude that allogeneic stem cell transplantation can be safely performed in some environments without confining patients continuously to the hospital.

Superior autologous blood stem cell mobilization from dose-intensive cyclophosphamide, etoposide, cisplatin plus G-CSF than from less intensive chemotherapy regimens.

The study purpose was to determine if G-CSF plus dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2 and cisplatin 105 mg/m2 (DICEP) results in superior autologous blood stem cell mobilization (BSCM) than less intensive chemotherapy. From January 1993 until May 1997, 152 consecutive patients with non-Hodgkin's lymphoma (n = 55), breast cancer (n = 47), Hodgkin's disease (n = 14), multiple myeloma (n = 9), AML (n = 9), or other cancers (n = 18) initially underwent BSCM by one of three methods: Group 1: G-CSF alone x 4 days (n = 30). Group 2: disease-oriented chemotherapy, dosed to avoid blood transfusions, followed by G-CSF starting day 7 or 8, and apheresis day 13 or 14 (n = 82). Group 3: DICEP days 1-3, G-CSF starting day 14, and apheresis planned day 19, 20 or 21 (n = 40). A multivariate analysis was performed to determine which factors independently predicted BSCM. The median peripheral blood CD34+ (PB CD34+) cell count the morning of apheresis linearly correlated with the number of CD34+ cells removed per litre of apheresis that day. The median PB CD34+ cell count and median CD34+ cells x 10(6) removed per litre of apheresis were highest for Group 3, intermediate for Group 2, and lowest for Group 1. By multivariate analysis, mobilization group (3 > 2 > 1), disease other than AML, no prior melphalan or mitomycin-C, and less than two prior chemotherapy regimens predicted better BSCM. Out of 15 Group 3 patients who had infiltrated marrows, 11 had no detectable cancer in marrow and apheresis products after DICEP. These data suggest that DICEP results in superior BSCM than less intensive chemotherapy regimens.

Allogeneic blood stem cell and bone marrow transplantation for acute myelogenous leukemia and myelodysplasia: influence of stem cell source on outcome.

We have compared the outcomes of 87 patients with acute myelogenous leukemia (AML) and myelodysplasia (MDS) receiving matched sibling transplants with stem cells from peripheral blood (blood cell transplant, BCT) or bone marrow (BMT). In good risk patients (AML in CR1) granulocytes recovered to 0.5 x 10(9)/l a median of 14 days after BCT compared with 19 days after BMT (P < 0.0001). For patients with poor risk disease (AML beyond CR1 and MDS) corresponding figures were 16 vs 26 days (P < 0.0001). Platelet recovery to 20 x 10(9)/l was also faster after BCT (good risk 12 vs 20 days, P < 0.0001; poor risk 17 vs 22 days, P = 0.04). Red cell transfusions were unaffected by cell source, but BCT recipients required less platelet transfusions (good risk 1 vs 5, P = 0.002; poor risk 5 vs 11, P = 0.004). Blood cell transplants resulted in more chronic GVHD (86% vs 48%, P = 0.005) and a significantly higher proportion of recipients with KPS of 80% or less (48% vs 5%, P = 0.004). Disease-free survival at 4 years was 23% for both groups of poor risk patients but outcome in good risk patients was better after BCT (93% vs 62%, P = 0.047) related mainly to less relapse. While disease-free survival may be better after BCT than BMT for AML in CR1, quality of life may be relatively impaired.

Single-agent high-dose melphalan salvage therapy for Hodgkin's disease: cost, safety, and long-term efficacy.

BACKGROUND: Few data are available on the cost, safety, and long-term efficacy of single-agent high-dose melphalan (HDM) followed by autologous bone marrow (ABMT) or blood stem cell (ABSCT) transplantation in the salvage therapy of Hodgkin's disease (HD). PATIENTS AND METHODS: From February 1981 to September 1996, 23 patients with relapsed (n = 15) or refractory (n = 8) HD received salvage therapy with HDM 140-200 mg/m2 followed by non-cryopreserved ABMT (n = 18) or cryopreserved ABSCT (n = 5). The cost of HDM/ABSCT in 1996, from initial consultation until transfer back to referring physician, was determined and compared to the estimate costs of two multi-agent regimens commonly used for HD. RESULTS: HDM was well tolerated with no early transplant-related mortality. The five-year overall and progression-free survival rates were 52% and 50%, respectively. The average total cost in Canadian funds of HDM/ABSCT in 1996 was $34,400/patient. This cost was estimated to be $4,700-6,800 cheaper per patient than the multi-agent high-dose regimens. CONCLUSION: These data suggest that HDM is safe, feasible, active, and reasonably inexpensive salvage therapy for patients with relapsed/refractory HD.

Addition of low-dose folinic acid to a methotrexate/cyclosporin A regimen for prevention of acute graft-versus-host disease.

A study was performed to determine whether the addition of folinic acid to a combination of methotrexate (MTX) and cyclosporin A (CsA) after allogeneic bone marrow transplantation (BMT) could improve tolerance to the regimen without inhibiting its ability to prevent graft-versus-host disease (GVHD). Sixty-nine adult BMT patients received CsA plus MTX 15 mg/m2 on day 1 and 10 mg/m2 on days +3, +6 and +11. Folinic acid 5 mg was started 24 h after each MTX dose and continued 6 hourly until 12 h before the next dose of MTX. The median age of the group was 37 years and 13 patients (19%) received bone marrow from mismatched and/or unrelated donors. No MTX doses were omitted or modified. Grade II-IV acute GVHD occurred in 18 patients (29%) and chronic GVHD in 35 of 56 (64%) patients at risk. There were no cases of grade > or = III stomatitis. Transplant-related mortality was 7% before 100 days and 20% overall (9% for low risk leukaemia) with a median follow-up of 41 months (range 24-88 months). This regimen of folinic acid rescue may contribute to a well tolerated GVHD prophylaxis protocol with reasonably low BMT-related mortality. Our results suggest that the ability of MTX to prevent acute GVHD is not abrogated by folinic acid given in this way.

Expression of multiple beta 1 integrins on circulating monoclonal B cells in patients with multiple myeloma.

We have previously reported the presence of monoclonal, tumor-related B lineage cells in the blood of myeloma patients. The cells are continuously differentiating, and the majority are at a very late stage of B cell differentiation into plasma cells, consistent with the hypothesis that they comprise a precursor cell subset responsible for disseminating and possibly for relapse of the disease. The pattern of beta 1 integrin expression on monoclonal B lineage cells from blood and bone marrow of myeloma patients was evaluated using multiparameter flow cytometry in comparison to normal blood or tissue B cells and malignant B cells from B-CLL, B lymphoma, or plasma cell leukemia. The alpha 4 and beta 1 chains were found on the majority of normal B cells, usually with a higher expression of alpha 4 compared to beta 1. alpha 5 was detectable at low density on B cells from lymph node, bone marrow, and lamina propria. the alpha 2 and alpha 6 chains are absent on B cells localized in normal lymphoid tissues as well as on normal blood B cells and in vitro activated B cells. In myeloma, the blood B cells express alpha 2, alpha 5, and alpha 6, suggesting important functional differences between these tumor-related B cells and their normal counterparts. The plasma cells located in myeloma bone marrow express no alpha 2, and almost no alpha 6, although they have variable expression of alpha 4, alpha 5, and beta 1. Thus the end-stage plasma cells appear to lack receptors that would support a propensity for invasion of basement membranes and exit to extravascular spaces. In contrast, the circulating plasmablasts in a patient with plasma cell leukemia make up a large subset of early plasma cells expressing all integrin receptors analyzed, including alpha 2 and alpha 6. Malignant cells from B-CLL and B lymphoma express only the alpha 4 and beta 1 integrins, and some B-CLL have very low levels of alpha 3, but no alpha 2, alpha 5, or alpha 6, suggesting that they may be limited to the vascular spaces and do not extravasate, at least for the stages of disease analyzed here.(ABSTRACT TRUNCATED AT 400 WORDS)

Restricted expression of immunoglobulin light chain mRNA and of the adhesion molecule CD11b on circulating monoclonal B lineage cells in peripheral blood of myeloma patients.

Circulating monoclonal B cells in peripheral blood from patients with multiple myeloma or with monoclonal gammopathy of undetermined significance (MGUS) have previously been shown to express CD19, CD20, and PCA-1 and are predominantly CD45R0+, characterizing them as very late stage B cells. This work shows that the abnormal B cells are monoclonal as defined by their exclusive expression of either kappa or lambda light chain mRNA, and that the same type of light chain mRNA is expressed in both bone marrow plasma cells and blood B cells. These abnormal tumour-related circulating B cells express high densities of CD11b, a beta 2-integrin, which is expressed in a conformationally active state as defined by reactivity with monoclonal antibody 7E3. Normal peripheral blood B cells which do not bear CD11b acquire a high density after stimulation with pokeweed mitogen (PWM). At day 4 of culture, the expression of CD11b on normal CD19+ B cells was nearly comparable to that of the circulating myeloma late stage B cells. After PWM stimulation of circulating myeloma B cells the expression of CD11b was gradually lost during 4 days of culture, suggesting that its expression is dynamically regulated. Two patients with no phenotypically abnormal B cells in their blood at diagnosis acquired a large subset of CD11b+ B cells 4 weeks after initiation of chemotherapy. In most patients, a subset of the circulating myeloma B cells express a low density of CD5. The proportion of CD19+ B cells in the bone marrow expressing CD11b was much reduced compared with peripheral blood B cells, and CD11b was not detectable on plasma cells in the bone marrow, suggesting a sequential relationship of the B-cell subsets detected in our population of patients, involving gradual loss of CD11b concurrent with the loss of CD19 during B lineage differentiation. These cells appear to represent a continuously differentiating monoclonal B lineage culminating in the CD11b- plasma cell entrenched in the bone marrow. We speculate that the expression of conformationally active CD11b on the abnormal B cells in peripheral blood mononuclear cells of myeloma patients facilitates transendothelial migration of circulating myeloma B cells to the bone marrow.

Allogeneic bone-marrow transplantation without protective isolation in adults with malignant disease.

Bone-marrow transplant (BMT) patients are severely immunocompromised immediately after the procedure and they are commonly nursed in strict protective isolation to reduce the risk of both infection and graft-versus-host disease (GvHD). We have studied a consecutive series of patients to see whether protective isolation is of benefit as prophylaxis against infectious complications of BMT. 50 consecutive patients who had malignant disease and received their first BMT from siblings or unrelated donors were nursed in standard single rooms with visitors instructed to wash their hands. A subset of 20 patients living locally spent a median of 25 days in hospital after BMT; they also spent some time at home on a median of 8 days before engraftment and 3 patients went home on more than 90% of their hospital days. 16 patients (32%) had positive bacterial cultures and/or focal infection. Gram-positive bacteraemia was found in 12 subjects (24%) but there were no gram-negative or deep fungal infections. Grade II or III acute GvHD developed in 17 patients (34%). There were no deaths from infection or acute GvHD. Transplant-related mortality was 6% in the first 100 days and 18% overall with a median follow-up of 22 months. Our mortality data compare favourably with those from institutions with strict isolation procedures. We conclude that BMT may be safely completed in some institutions without either protective isolation or the need to confine patients continuously in hospital.

Red blood cell alloimmunization complicating plasma transfusion.

Well-known adverse effects of plasma transfusion include viral transmission, allergic complications, and rare anaphylactic reactions. In making clinical decisions to transfuse plasma, a seldom-considered complication is that of red blood cell (RBC) alloimmunization. The authors report a patient in whom strong IgM and IgG anti-E and weak IgG anti-JKa RBC antibodies developed 15 days after infusion of two units of fresh-frozen plasma for volume expansion. These antibodies are potentially hemolytic. This case underscores the importance of considering risks of plasma infusion. Plasma should not be used casually, especially for indications for which alternate therapies, such as crystalloid and colloid solutions, are available.

Selective expression of CD45 isoforms defines CALLA+ monoclonal B-lineage cells in peripheral blood from myeloma patients as late stage B cells.

The peripheral blood lymphocytes from 42 patients with multiple myeloma (MM) and 13 patients with monoclonal gammopathy of undetermined significance (MGUS) were studied by three-color immunofluorescence (IF) using antibodies directed to a broad range of B-cell markers (CD19, CD20, CD21, CD24), CALLA (CD10), PCA-1 (a plasma cell marker), and to the high and low molecular weight isoforms of the leukocyte common antigen, CD45RA (p205/220) and CD45RO (p 180). CD45RA is expressed on pre-B and B cells, and a transition from CD45RA to CD45RO defines differentiation towards plasma cells. Peripheral blood mononuclear cells (PBMC) from patients with myeloma included a large subset of B-lineage cells (mean of 39% to 45%) that were CALLA+ and PCA-1+ in all patients studied, including newly diagnosed patients and patients undergoing chemotherapy. Southern blot analysis indicated the presence of monoclonal Ig rearrangements in PBMC and a substantial reduction in the germ-line bands consistent with the presence of a large monoclonal B-cell subset. Avoidance of purification methods involving depletion of adherent cells was essential for detection of the abnormal B cells. Phenotypically, this abnormal B-cell population corresponded to late B or early pre-plasma cells (20% to 80% of PBMC), as defined by the concomitant expression of low densities of CD19 and CD20, moderate densities of CALLA and PCA-1, and strong expression of CD45RO on all B cells, with weakly coexpressed CD45RA on a small proportion. Heterogeneity in the expression of CD45RA and CD45RO within the abnormal B-cell population from any given patient suggested multiple differentiation stages. Abnormal B cells similar to those in MM were also detected in MGUS, although as a lower proportion of PBMC (26%). Abnormal B cells from patients with MGUS expressed predominantly the CD45RO isoform, but had a lower proportion of CALLA+ and PCA-1+ cells than were found on B cells from MM. This work indicates that the large subset of circulating monoclonal B lymphocytes from myeloma patients are at a late stage in B-cell differentiation, continuously progressing towards the plasma cell stage.

Hemopoietic origin of factor XIII A subunits in platelets, monocytes, and plasma. Evidence from bone marrow transplantation studies.

Factor XIII A subunit (FXIIIA) is found in plasma, platelets, and monocytes. The hemopoietic contributions to FXIIIA in these components were studied in patients transplanted with marrows from donors with different FXIIIA phenotypes. In three patients with successful engraftment (by DNA genotyping, red cell phenotyping, and cytogenetic studies) platelet and monocyte FXIIIA changed to donor phenotypes with hematologic recovery. Thus, FXIIIA in platelets and monocytes is synthesized de novo and/or from their progenitor cells. Plasma FXIIIA phenotype change after transplantation was more complex. Patient I changed from phenotype 1-1 (one electrophoretically fast band) to 1-2 (three bands) in 115 d; patients 2 and 3 did not change completely from phenotype 1-2 to 1-1 in up to 458 d, but did show enrichment of the fastest band. Thus, while there is a definite contribution of donor hemopoiesis to plasma FXIIIA, another source of recipient FXIIIA appears to be present to delay or prevent the phenotype change.

Treatment of advanced Hodgkin's disease with high dose melphalan and autologous bone marrow transplantation.

Twenty patients with Hodgkin's disease which had relapsed at least once after chemotherapy, were treated with melphalan 140-220 mg/m2 i.v. followed by reinfusion of non-cryopreserved autologous bone marrow. Four patients (20%) remain alive and disease-free 28, 45, 52, and 96 months after treatment respectively. There were no treatment-related deaths. This appears to be the only reported series of patients treated with a single agent in this situation. The results are comparable to those achieved by multi-agent regimens with autologous or allogeneic bone marrow transplantation.

Abnormalities in lymphocyte profile and specificity repertoire of patients with Waldenstrom's macroglobulinemia, multiple myeloma, and IgM monoclonal gammopathy of undetermined significance.

The characteristics of T and B lymphocyte profile and B lymphocyte specificity repertoire were compared in patients with Waldenstrom's macroglobulinemia (WM), IgM monoclonal gammopathy of undetermined significance (IgM MGUS), multiple myeloma (MM), and age-matched normal subjects. Patients with MM had both significantly reduced frequency and number of sIg+ (surface Ig) B cells, whereas patients with WM and IgM MGUS had a reduced frequency but normal numbers of sIg+ B cells in circulation as detected in a capping assay. WM was distinguished by the large numbers of cells in the peripheral blood lymphocyte (PBL) pool that expressed CD9 (BA-2) and CD24 (BA-1) and were monoclonal, based on light chain analysis using flow cytometry. The profile of T lineage cells showed that the ratio of CD4:CD8 was significantly reduced in both MM and WM due to a reduction in the CD4 set. The CD4+ cells were qualitatively abnormal as well, with an enriched proportion of the 4B4+ (CDw29) subset and decreased proportion of the Lp220+ (CD45R) subset. This appeared to be an effect of the disease process on the relatively immature Lp220+ set. From clonal analysis, those patients with WM or IgM MGUS (unlike MM patients) did not exhibit enhanced reactivity with auto-Ig determinants, and most WM patients (7/8) and half of the IgM MGUS patients (3/6) did not have enriched proportions of B cells reactive to tetanus toxoid (TT). The TT-specific B cells in both WM and IgM MGUS, in contrast to MM, appeared fully functional in secretion of anti-TT IgM in vivo. We speculate that the more severe immunodeficiency in MM may be controlled or exacerbated by the presence of an anti-Ig network. The absence of this network in WM allows a relatively more effective immune response, but the immunodeficiency that is observed in these patients involves some abnormality in normal lymphocyte differentiation (is also present in MM).

Comparative analysis of immunodeficiency in patients with monoclonal gammopathy of undetermined significance and patients with untreated multiple myeloma.

The objectives of this study were firstly, to compare the immunophenotype of patients with monoclonal gammopathy of undetermined significance (MGUS) with that of patients with newly diagnosed, untreated multiple myeloma (Unt. MM). Our second objective was to determine which variables might distinguish patients with MGUS and early MM. The CD4/CD8 ratio in both patient groups differed significantly from normal as a result of a decrease in the proportion of CD4+ cells. Similarly, surface immunoglobulin-positive (Ig+) B cells were significantly reduced in both groups. Also, some impairment of Ig secretion was observed. An in vitro specificity study of B cells showed an enriched proportion of B cells specific for tetanus toxoid (which may be indicative of enrichment for memory B cells) in both MGUS and Unt. MM patients. Further to this, in MM patients but not in MGUS patients, there was an enriched proportion of B cells specific for determinants on the F(ab')2 fragment of Ig. This suggests an anomalous auto-immune reactivity to polyclonal Ig molecules. In one of the two patients studied, who progressed from MGUS to MM, disease progression was accompanied by an increase in this anti-Ig reactivity. In both patients there was a decrease in CD4/CD8 ratio.

Double autologous bone marrow transplantation for acute myelogenous leukemia in a patient treated for Hodgkin's disease.

A 30-year-old man developed acute myelogenous leukemia nearly 3 years after treatment of Hodgkin's disease with radiation and three chemotherapy combinations. Remission was induced with one cycle of high-dose Ara-C therapy. Three cycles of consolidation chemotherapy were given. The patient then had two autologous bone marrow transplants, the first after conditioning with 5 Gy total body irradiation, the second after Melphalan 140 mg/m2. The procedures were well tolerated, although hematological reconstitution was very slow after the second autotransplant. The patient has been disease-free for over 4 years. Such patients may be more vulnerable to transplant-related complications because of their previous exposure to chemotherapy and radiation, which may damage several organs including the bone marrow. This report demonstrates that patients with secondary acute myelogenous leukemia may tolerate a double autotransplant procedure and achieve durable remissions.

Biochemical classification of circulating immune complexes in human malignant melanoma and hematologic neoplasms.

Circulating immune complexes (CIC) in human cancer are known to be very heterogeneous in size and composition. In 95 staged malignant melanoma patients and 71 individuals with leukemia and lymphoma, this heterogeneity was analyzed biochemically in sera positive for CIC. CICs were measured by a multiassay system and individual complexes were isolated and analyzed by immunological and biochemical methods. Analyses of sera from 100 normal individuals, from 25 rheumatoid women, and a group of 12 laboratory staff who work with human melanoma were included for comparison. Three basic patterns of complexes were identified circulating in the sera of the cancer patients. Type I are medium-sized (17-23S), complement-fixing complexes usually occurring in combinations. The prototype in melanoma contained IgG antibody and additional glycoprotein components and bound complement by the classical pathway. In hematological malignancies four subtypes could be identified depending on whether the antibody class was IgG or IgM, the nonimmunoglobulin component was glycoprotein or protein, and whether complement fixation occurred by the classical or alternate pathway. Type II complexes were noncomplement-fixing, medium-sized complexes (15-21S), which in melanoma contained IgG antibody and additional protein components. In the hematologic malignancies two subtypes could be identified depending on whether the antibody class was IgG or IgM. Both subtypes contained a glycoprotein nonimmunoglobulin component. Both melanoma and hematologic tumors had type III heavy complexes (36-44S) which were noncomplement-fixing and contained only immunoglobulin components, either IgG-IgG or IgM-IgG. As expected the rheumatoid arthritis patients frequently had both 7S and 21-23S CICs containing IgG as well as IgM rheumatoid factor with complement fixation via the classical pathway. No CICs were detected in normal young men and women (20-30 years); a few individuals in middle age (31-50 years) had small (7-11S) CICs which bound complement by the classical pathway and contained IgG and a protein nonimmunoglobulin component. The frequency of these 7S complexes increased with advancing age, with the appearance of 23S IgG-IgG or IgM-IgG complexes. IgG antibodies from only the melanoma patients reacted with cytoplasmic components of fresh melanoma cells, except the laboratory workers where all of their isolated CIC antibodies also reacted with melanoma cells. Thus the heterogeneity of complexes in melanoma is not random, but can be classified into three basic biochemical patterns. The hematologic group provides a slightly richer variation of subtypes within this basic scheme.

Staging laparotomy in Hodgkin's disease: a community hospital experience.

Between 1977 and 1984, 50 patients with Hodgkin's disease underwent a staging laparotomy performed by nine surgeons in a community hospital. Adequate procedures were performed in 80% of cases compared to staging laparotomies done between 1969 and 1976 when only 40% were properly performed. Abdominal lymphangiogram had a false-negative rate of 0 but a false positive rate of 70%. Clinical stage III disease was significantly downstaged at laparotomy (65% of cases). Postoperative complication rate was 4% and there were no operative deaths. A subset of patients not requiring laparotomy have been identified. Because the quality of staging laparotomy and lymphangiography was variable, we encourage all centres treating patients with Hodgkin's disease to review their own experience with these techniques before making individual patient treatment decisions.

Selective loss of CD4+ CD45R+ T cells in peripheral blood of multiple myeloma patients.

The phenotypic distribution of T-lymphocyte subsets in peripheral blood from multiple myeloma (MM) patients shows a reduced proportion of CD4+ cells and a normal proportion of CD8+ cells. The decrease in CD4+ cells could be due to a random process, with all types of CD4+ cells being equally affected, or it could reflect a nonrandom process with selected subsets preferentially reduced. In order to distinguish between these possibilities, double immunofluorescence analysis was performed on blood samples from patients with MM, patients with monoclonal gammopathy of unknown significance (MGUS), and age-matched normal donors, using monoclonal anti-CD4 or anti-CD8 paired with antibodies to the common leukocyte marker Lp220 (CD45R) or 4B4 (CDw29). Normal peripheral blood lymphocytes (PBL) include two phenotypically and functionally distinct CD4+-cell subsets, identified as CD4+ Lp220+ 4B4- and CD4+ Lp220-4B4+, whereas the majority of CD8+ cells expresses Lp220 (70-85%). MM patients had a highly significant selective reduction of the CD4+ Lp220+ subset compared with normal controls (P less than 0.001). Although the percentage of CD4+ Lp220- cells was also reduced in some MM patients relative to normal donors, most of MM patients had an elevated Lp220-/Lp220+ ratio of CD4+ cells (P less than 0.001). The proportion of the two CD8+ subsets was also markedly abnormal. In the set of patients studied the abnormalities within the CD4+ and CD8+ lymphocytes were exclusive to patients with MM since patients with MGUS had normal proportion of CD4+ and CD8+ subsets.