Cases Of Chronic Lymphatic Leukemia Research Articles

PB2065 DIAGNOSTIC VALUE OF THE NEW SYSMEX XN 2000 AUTOANALIZER IN THE STUDY OF LYMPHOCYTOSIS

Background:The new Sysmex analyzers of the XN series (Sysmex Corporation, Kobe, Japan) incorporate new leucocytes channels (WNR, WPC or WDF) based on fluorescence flow cytometry. Fluorescence flow cytometry, through these channels, enables separation of different leukocyte populations and generates numerous cellular parameters. The FSC (forward light scatter) intensity is proportional to the cell size, the SSC (side light scatter) to cellular complexity (granularity) and the SFL (lateral fluorescent light) to DNA/RNA content of the cells (nucleus). Several flags (QFLAGS) alert of blasts, abnormal (ABN) lymphocytes (neoplastic) and atypical (ATYP) lymphocytes (reactive) have been developed based on the cells scatter light behavior. High fluorescence lymphocytes (HPLC) can also be quantified. Moreover, Syxmex XN analyzers incorporate non‐routine parameters, such as those of the lymphocyte populations: three related to the midpoint LY‐X (the lateral scattered light intensity), LY‐Y (the fluorescent light intensity), LY‐Z (the FSC intensity); and three with the distribution area LY‐WX (the lateral scattered light distribution width) LY‐WY (the fluorescent light distribution width) and LY‐WZ (the FSC distribution width). In a previous study, we observed that the lymphocyte parameters and the alarms of Sysmex‐XN (age, number of lymphocytes, Q‐FLAG, LY‐Z, and LY‐WZ) are useful tools to guide the diagnosis of lymphocytosis with an overall diagnostic value 87%1.Aims:To determine the diagnostic value of these parameters obtained in a previous study 1in a different population of lymphocytosis.Methods217 new cases with lymphocytosis > 4.0 × 109/l were recruited. A peripheral blood immunophenotype (IF) was performed to distinguish polyclonal (n = 144) and monoclonal (n = 73) lymphocytosis. This study also allowed the separation of 33 cases of chronic lymphatic leukemia (LLC), 18 cases of LLC zap70 + and 22 marginal lymphomas.All the samples were analyzed with the XN‐2000 for WDF and WPC channels. The diagnostic value of the statistically significant variables obtained from a previous study 1, including Age> 60 years; Lymphocytes> 7 × 10E9/L and> 12 × 10E9/L; QFLAG ATYP + ABN> 205 and> 345; LY‐Z> 64,> 65 and> 67; LY‐WZ> 590 were applied in this new group of samples.Results:When we consider age (60years) as a cut‐off point, in the group <60 years we only observed 3 cases with monoclonal lymphocytosis, which was considered unrepresentative.In the group >60 years we observed 71 polyclonal and 70 monoclonal lymphocytosis (table). XN‐based parameters showed a global classification value of 83%. Regarding monoclonal lymphocytosis, 54 of the 70 patients (77%) were correctly classified. The most predictive variables of clonal lymphocytosis were QFLAG ABN + ATYP (PPV 83%) and absolute lymphocyte count > 7 × 109/L (PPV 72%).Summary/Conclusion:The results were similar to our previous study and confirmed the utility of these parameters in an initial study of lymphocytosis. The positivity of these variables had a high predictive value of monoclonal lymphocytosis. Therefore, it could be used as a routine practice in laboratories.image

Aggressive cutaneous vasculitis in a patient with chronic lymphatic leukemia following granulocyte colony stimulating factor injection: a case report

IntroductionVasculitis has been reported in a few cases of chronic lymphatic leukemia and with granulocytic colony-stimulating factor therapy. Those with granulocytic colony-stimulating factor occurred after prolonged therapy and there was a rise in total leukocyte count unlike that in our patient who received just a single injection for the first time.Case presentationWe report the case of a 64-year-old Egyptian man with chronic lymphatic leukemia who developed progressive cutaneous vasculitic lesions following injection of a single dose of a granulocytic colony stimulating factor before a third cycle of chemotherapy to improve neutropenia. This is an unusual case and the pathogenesis is not fully understood. Our patient was not on any medical treatment except for bisoprolol for ischemic heart disease. Although aggressive management with steroids, anticoagulation and plasmapheresis had been carried out, the condition was aggressive and the patient's consciousness deteriorated. A magnetic resonance imaging scan of his brain revealed multiple ischemic foci that could be attributed to vasculitis of the brain.ConclusionThe aim of this case report is to highlight the importance of monitoring patients on granulocytic colony-stimulating factor therapy, especially in the context of other conditions (such as a hematological malignancy) that may lead to an adverse outcome.

Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications for antibody selection

AbstractRituximab, a monoclonal antibody that targets CD20 on B cells, is now central to the treatment of a variety of malignant and autoimmune disorders. Despite this success, a substantial proportion of B-cell lymphomas are unresponsive or develop resistance, hence more potent anti-CD20 monoclonal antibodies (mAbs) are continuously being sought. Here we demonstrate that type II (tositumomab-like) anti-CD20 mAbs are 5 times more potent than type I (rituximab-like) reagents in depleting human CD20 Tg B cells, despite both operating exclusively via activatory Fcγ receptor–expressing macrophages. Much of this disparity in performance is attributable to type I mAb-mediated internalization of CD20 by B cells, leading to reduced macrophage recruitment and the degradation of CD20/mAb complexes, shortening mAb half-life. Importantly, human B cells from healthy donors and most cases of chronic lymphatic leukemia and mantle cell lymphoma, showed rapid CD20 internalization that paralleled that seen in the Tg mouse B cells, whereas most follicular lymphoma and diffuse large B-cell lymphoma cells were far more resistant to CD20 loss. We postulate that differences in CD20 modulation may play a central role in determining the relative efficacy of rituximab in treating these diseases and strengthen the case for focusing on type II anti-CD20 mAb in the clinic.

Leukemia incidence among people exposed to chronic radiation from the contaminated Techa River, 1953–2005

Beginning in 1950, people living on the banks of the Techa River received chronic low-dose-rate internal and external radiation exposures as a result of releases from the Mayak nuclear weapons plutonium production facility in the Southern Urals region of the Russian Federation. The Techa River cohort includes about 30,000 people who resided in riverside villages sometime between 1950 and 1960. Cumulative red bone marrow doses range up to 2 Gy with a mean of 0.3 Gy and a median of 0.2 Gy. Between 1953 and 2005, 93 first primary cases of leukemia, including 23 cases of chronic lymphatic leukemia (CLL), were ascertained among the cohort members. A significant linear dose-response relationship was seen for leukemias other than CLL (P < 0.001), but not for CLL. The estimated excess relative risk per Gy is 4.9 (95% confidence interval (CI): 1.6; 14.3) for leukemias other than CLL and less than 0 (95% upper bound 1.4) for CLL.

Safety and efficacy of hematopoietic stem cell collection from mobilized peripheral blood in unrelated volunteers: 12 years of single-center experience in 3928 donors

AbstractWe present results of peripheral blood stem cell (PBSC) mobilization, collection, and follow-up from 3928 consecutive unrelated stem cell donors. Assessments were performed prospectively at baseline, leukapheresis, 1 month, 6 months, and annually after PBSC donation. During follow-up, side effects were recorded by return post questionnaires. The median CD34+ cell counts on day 5 were 67.5/μL in male and 51/μL in female donors. Bone pain and headache were the most common side effects of recombinant human granulocyte-colony stimulating factor. Central venous access was required for 23 donations (0.6%). Throughout the follow-up, the absolute neutrophil counts were slightly below the initial baseline values but remained within the normal range. The majority of the donors reported good or very good health. Malignancies occurred in 12 donors (0.3%), among whom were 1 case of acute myeloid leukemia, 1 case of chronic lymphatic leukemia, and 2 cases of Hodgkin disease. Only the incidence of Hodgkin lymphoma differed significantly from an age-adjusted population. In conclusion, 7.5 μg/kg per day lenograstim proved to be safe and effective for mobilizing hematopoietic stem cells for allogeneic transplantation. Long-term monitoring of healthy PBSC donors remains important to guarantee the safety standards of PBSC mobilization and collection.

Abstract A88: Body mass index, height, and risk of lymphatic malignancies: A prospective cohort study

Abstract A88 Introduction Several studies have observed that body mass index (BMI) is associated with an increased risk of lymphatic malignancies (LM) or with one of its subgroups. Other studies have not observed an association, and the results are therefore inconclusive. Very few studies have investigated whether BMI around age 20 and height are associated with LM risk. We investigated therefore the association between BMI, BMI at age 20 and height and the risk of LM in a prospective cohort study. Methods In 1986, the Netherlands Cohort Study on Diet and Cancer (NLCS) was initiated. A self-administered questionnaire on diet and other risk factors for cancer was completed by 120,852 men and women, aged 55-69 at baseline. Data were processed and analyzed using the case-cohort approach, enumerating the cases for the entire cohort, and estimating the person years at risk in the cohort using a subcohort. This subcohort was randomly sampled from the entire cohort immediately after the baseline measurement and is being followed up for vital status. Cohort members who reported cancer at baseline were excluded from analysis. Follow-up for cancer was established by annual record linkages with the Netherlands Cancer Registry and the nationwide pathology registry. After 13.3 years of follow-up, data regarding from 1,042 LM cases and from 4,588 subcohort members were available for analysis. Using the histology codes provided by the cancer registries and the abstracts provided by the pathology registry, the LM cases were subdivided into categories based on the third edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. There were 232 cases of diffuse large-cell lymphoma (DLCL), 79 cases of follicular lymphoma (FL), 71 cases of Waldenström macroglobulinemia/ immunocytoma (WMI), 171 cases of chronic lymphatic leukemia (CLL), and 291 cases of multiple myeloma (MM). Other subgroups were too small (N&amp;lt;70) for analysis. Rate ratios (RRs) were estimated using the Cox proportional hazards model, with multivariate adjustment for confounders. Results BMI at baseline was not associated with LM risk, the RR per increment of 4 kg/m2 was 1.03 (95% confidence interval (CI): 0.94-1.13). RRs were not different between males and females. BMI at baseline was not associated with increased risk of any of the LM subtypes. BMI around age 20 was associated with LM risk overall (RR per 4 kg/m2 increment 1.13; 95% CI: 1.01-1.25), with DLCL risk (RR 1.20; 95% CI: 0.98-1.47) and WMI risk (RR 1.41; 95% CI: 1.01-1.95). The association between BMI around age 20 and LM risk was higher in males (RR per increment of 4 kg/m2 increment: 1.22; 95% CI: 1.03-1.44) than in females (RR: 1.05; 95% CI: 0.91-1.21). Height was positively associated with LM risk: the RR for 5 cm increment was 1.08 (95% CI: 1.02-1.15) for LM overall. The association between height and LM risk was higher in females (RR per increment of 5 cm: 1.14; 95% CI: 1.04-1.24) than in males (RR: 1.05; 95% CI: 0.89-1.13). For the DLCL subtype, the RR was 1.19 (95% CI: 1.07, 1.33). Conclusion The positive associations between both BMI at age 20, height and the risk of LM suggest that exposures during early life play a role in the etiology of LM. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A88.

Fever of unknown origin: Chronic lymphatic leukemia versus lymphoma (Richter’s transformation)

Currently, malignancies are more common than infections as a cause of fever of unknown origin (FUO) in adults. Many malignant disorders are associated with fever, which may either be of the hectic-septic variety resembling an infectious disease or prolonged and low-grade. Neoplasms with either kind of fever may present as an FUO. The malignancies usually associated with fever are lymphoreticular malignancies involving the blood, liver, spleen, or bone marrow. Most malignancies do not have fever, e.g., chronic lymphatic leukemia (CLL), as part of their clinical presentation. We present a case of long-standing CLL in an elderly woman who presented with an FUO. Initially, it was thought that her FUO was caused by CLL or a CLL-related opportunistic infection. The naprosyn test was used in this patient with CLL and FUO to differentiate a malignant from an infectious etiology. Her response to naprosyn indicated that the etiology of her FUO was neoplastic rather than infectious. The absence of tonsillar enlargement and peripheral adenopathy, as well as the presence of fever, argued against CLL as the cause of her fever. Computed axial tomography scans showed central adenopathy in addition to splenomegaly. The presence of fever, splenomegaly, and central adenopathy indicated that the cause of her FUO was a lymphoma (Richter's transformation) and not CLL.

Immunophenotype of hairy-cell leukaemia after cold polymerization of methyl-methacrylate embeddings from 50 diagnostic bone marrow biopsies.

Hairy-cell leukaemia may be difficult to diagnose in bone marrow biopsies, especially in the early stages or in its residum after complete clinical remission. To consider the impact of published data on immunophenotyping hairy-cell leukaemias, a total of 50 diagnostic biopsies were systematically analysed with a panel of eight antibodies and compared with cases of chronic lymphatic leukaemia (CLL), 20 follicular centre lymphomas, 20 lympho-plasmacytoid immunocytomas, 10 small-cell T-cell non-Hodgkin lymphomas and 20 cases of benign nodular lymphatic hyperplasia. The panel of eight antibodies comprised DBA44, CD45, CD20, CD45R, CD45RO, CD43 and the CD68 antibodies KP1 and Ki-M1P. The hairy-cell leukaemias were staged histologically into four categories of bone marrow infiltration. DBA44 reacted positively in 47/50 cases. CD45 and the B-cell markers CD20 and CD45R reacted in 49/50 and 43/50 cases, respectively. One CD68 marker, KP1, was positive in 38/50 cases but the other-Ki-M1P-only in 1/50 cases. Chronic lymphatic leukaemia cases, the other B-cell NHLs and lymphatic hyperplasias showed strong positivity for CD20 and CD45R, but only the immunocytomas reacted with DBA44 in 7/20 cases. The T-cell NHLs and hyperplasias showed a strong positivity for the T-cell markers CD45RO and CD43. The CD68-marker Ki-M1P revealed a high specificity since it was negative in all NHLs and positive only in one hairy-cell leukaemia. Methyl-methacrylate embedding of bone marrow biopsies under cold polymerization produces a high quality of histo- and cytomorphology, resulting in greater diagnostic reliability and the detection of low-stage infiltration of hairy-cell leukaemia. DBA44 appears as a highly specific antibody to mark hairy-cells since only immunocytomas reacted positively in a few cases. A small panel of antibodies including DBA44. CD20, CD45R and Ki-M1P may serve to distinguish small-cell. NHL from hairy-cell leukaemia even at an early stage or when there are minimal residual tumour cells.

Observation of Surface Markers on Leukemic Cells in Three Cases of Chronic Lymphatic Leukemia

Observation of Surface Markers on Leukemic Cells in Three Cases of Chronic Lymphatic Leukemia

Immunoperoxidase staining of surface and intracellular immunoglobulin in human neoplastic lymphoid cells.

An immunoperoxidase technique for the optical microscopic detection of cellular immunoglobulin has been used to stain fixed smears of human neoplastic B lymphoid cells. Only four out of 28 cases of chronic lymphatic leukaemia (CLL) showed membrane labelling by this technique. In contrast, when 14 samples from other types of B lymphoproliferative disorder (including hairy cell leukaemia, non-Hodgkin's lymphoma, and prolymphocytic leukaemia) were studied, all samples showed membrane immunoglobulin labelling (confirmed by capping experiments). This discrepancy was attributed to the greater density of surface immunoglobulin present on neoplastic cells in the latter group of disorders compared to CLL. This immunoperoxidase technique is therefore less sensitive than immunofluorescent staining of cells in suspension for the demonstration of neoplastic cell surface immunoglobulin. However, it offers a number of advantages (eg, excellent visualisation of cell morphology, permanence of stained preparations, and applicability to stored samples) which recommend it as the method of choice in certain clinical haematological contexts.

Evidence for a shift from IgD to IgA synthesis in the maturation of human B lymphocytes

A case of chronic lymphatic leukemia (CLL) is described in which IgD and IgA are the copredominant membrane immunoglobulins. Since CLL represents malignant proliferations of B lymphocytes arrested at discrete points during maturation, the findings in this case suggest that at least some of the developing cells destined to synthesize IgA for secretion pass through a stage in which immunoglobulins D and A are present together on the cell membrane.

SECONDARY LIPIDOSIS IN LEUKEMIA

Foam cells in the spleen, bone marrow, liver and lymph nodes were examined on the 73 reliably recorded and sampled leukemia autopsy cases encountered at Kobe University from 1958 to 1972. Although the substances stored in the foam cells were biochemically unknown, the foam cells in leukemia could be morphologically classified into two types: The one was identified with the Gaucher type, but the other was not identified with the sea-blue type and might be considered as to be the transitional type described in another report. Foam cells could be found in the spleen of 6 out of 12 cases of chronic myeloid leukemia, one out of 2 cases of chronic lymphatic leukemia, one out of 7 cases of leukemic lymphosarcoma, one out of 9 cases of acute lymphatic leukemia, and none in 3 cases of monocytic leukemia. In acute myeloid leukemia, the incidence of foam cells in the spleen was 47.5% in 40 cases, and acquired lipidoses were more frequently seen in cases under 19 years of age, in male cases, in cases with an enlarged spleen over 400 g, and in cases of over 4 months' duration.

Subpopulations of Human Lymphocytes Defined by β2-Microglobulin

Abstract A human serum protein with structural homology to immunoglobulins, β2-microglobulin, was synthesized by normal lymphocytes in vitro. Production of microglobulin was increased when lymphocytes were stimulated with phytohemagglutinin (PHA) or concanavalin A (Con A) but was not increased by stimulation with pokeweed mitogen, suggesting that microglobulin was elaborated by thymus-dependent lymphocytes. Maximal β2-microglobulin production occurred at a concentration of PHA (2 µg/106 cells) which was far lower than that which led to maximal DNA and protein synthesis. Treatment of normal lymphocytes in culture with anti-β2-microglobulin and complement removed 20% of the cells and abolished β2-microglobulin production while stimulation of DNA synthesis by PHA was only slightly decreased. Fluorescein coupled antibody to β2-microglobulin stained virtually all normal lymphocytes, but 15 to 20% stained brightly. Although 15 to 25% of normal lymphocytes stained with anti-light chain antibody, none of these cells stained brightly with antibody to microglobulin when double-staining experiments were performed with two fluorochromes. Lymphocytes from a patient with acquired agammaglobulinemia synthesized microglobulin at a normal rate although the thymus independent (B) cell population as determined by staining for immunoglobulin was less than 3%. On the other hand, synthesis of microglobulin by lymphocytes from four patients with stage IV Hodgkin's disease was minimal. Production of β2-microglobulin by peripheral lymphocytes of patients with chronic lymphatic leukemia (CLL) was low when the lymphocytes were identified as B-cells; synthesis was normal, however, by lymphocytes lacking surface immunoglobulin in one case of CLL. These results suggest that in man β2-microglobulin is in large part the product of a thymic dependent lymphocyte subpopulation.

Non-immunoglobulin-bearing 'B' lymphocytes in chronic lymphatic leukaemia?

Summary. Log‐normal ranges for the incidence of immunoglobulin‐bearing lymphocytes in human peripheral blood are described. Twenty‐five cases of chronic lymphatic leukaemia have been investigated and absolute numbers of cells have been ascertained and related to clinical details. It is suggested that most CLL patients suffer from a disorder of the B cell population, including many in which non‐immunoglobulin‐bearing cells predominate.

Antibody to Epstein-Barr virus and cellular immunity in Hodgkin's disease and chronic lymphatic leukemia.

AbstractAntibodies to Epstein‐Barr virus capsid antigen (VCA), early antigen (EA) and cellular immunity as measured by skin reactivity to keyhole limpet hemocyanin (KLH) and Brucella antigen (BA) were measured in 15 cases of Hodgkin's disease (HD) and 14 cases of chronic lymphatic leukemia (CLL) before treatment and one year later. Both groups of diseases were associated with elevated VCA and EA antibody levels when compared with 18 controls, and in both groups the mean titers were unchanged after therapy. A negative skin test to KLH was associated with a short survival in the HD group and was found more frequently in CLL patients with active disease. In the young HD patients, a higher EBV titer was found in pretreatment sera of non‐survivors compared with those who are still alive. There was no correlation, however, between tests for cell‐mediated immunity and humoral antibodies against EBV. The finding of similar titers in patients with depressed and normal skin reactivity indicates that the elevated titers are probably not the result of a non‐specifically depressed immune defense.

Clinical significance of abnormally shaped IgM arcs in serum immunoelectrophoresis

A series of 21 cases is described in which serum immunoelectrophoresis revealed an abnormally shaped IgM arc even though no paraprotein could be seen on simple electrophoresis. There were 9 cases of lymphoma, 5 cases of chronic lymphatic leukemia and 2 of hypernephroma. In order to demonstrate this phenomenon, careful attention must be paid to the immunoelectrophoretic technique. Immunoelectrophoresis can be of value in the diagnosis of lymphoproliferative disease in cases where simple electrophoresis gives no hint of a paraprotein.

Prognostic factors in chronic lymphatic leukaemia

It is well recognized that the morphology of the peripheral blood lymphocytes in chronic lymphatic leukaemia (CLL) may show considerable variation. Many cases have a proportion of cells with indented nuclei and or nucleoli. The records and blood films of 69 cases of CLL at presentation were reviewed to see if a relationship could be demonstrated between survival and the maturity of lymphocytes in the blood. At the same time cases of lymphosarcoma were reviewed in an attempt to define the common ground between this disease and CLL. Only two aspects of lymphocyte morphology were considered, the presence of nucleoli and deep nuclear clefts. The haemoglobin, white cell count, platelet count, ESR, the presence of lymphadenopathy and splenomegaly were recorded and the patients’ survival in months from diagnosis. Results were grouped according to lymphocyte morphology as shown: Mean survival (mth.) Mean survival (mth.) Nucleoli alone (13 cases) 26.5 Nucleoli (20 cases) 23.9 Nucleoli deep + clefts (7 cases) 19.3 Deep clefts alone (6 cases) 66.2 No nucleoli (49 cases) 44.4 Neither nucleoli nor deep clefts (43 cases) 41.3 The difference in survival between the group with deep clefts alone and the group without nucleoli or deep clefts was not statistically significant. These two groups were combined for comparison with all cases showing nucleoli. A highly significant difference was shown: (Wilcoxon rank test 2 α -= 0.01). Patients with presenting Hb 50 mmlhr.. or with platelets 3 survived less well than appropriate control groups (Wilcoxon rank tests 2 α = 0.01, 0.01 and 0.1 respectively). No relationship was seen between height of WBC count, presence of lymphadenopathy or splenomegaly and survival. Ten patients out of 47 with lymphosarcoma showed a lymphocytosis. Only one case showed nucleolated lymphocytes in the blood. The mean survival of these 10 patients was 35 mth. compared with 23 mth. for the group as a whole. The prognostic value of these findings was considered.

Leukocyte alkaline phosphatase: a quantitative and qualitative study in normal and leukemic cells.

Summary. Alkaline phosphatase was determined in pure preparations of granulocytes, lymphocytes, and different types of leukemic cells from subjects not yet given any treatment. In most cases of myeloid leukemia alkaline phosphatase activity was markedly reduced with respect to that of normal granulocytes: a modest degree of activity could be demonstrated in one case only. While no alkaline phosphatase could be demonstrated in normal lymphocytes, it was present, even if only in modest amounts, in two cases of chronic lymphatic leukemia. Electrophoretic fractionation consistently revealed in the granulocyte preparations a wide band with alkaline phosphatase activity extending from aa to the β-globulins, and a fainter band at the level of γ-globulins. In most of the electrophoretic strips of leukemic cells no phosphatase activity could be demonstrated; when present, the electrophoretic pattern was different from that of normal granulocytes, but it varied from case to case.

Serum calcium and phosphorus abnormalities in leukemia

The records of all cases of leukemia at the University of California Medical Center during the five year period from January 1960 to December 1964 were reviewed for data on serum calcium, phosphorus and alkaline phosphatase determinations and roentgenologic examination of the skeleton. A total of 260 cases were found, 123 of which included a calcium and phosphorus determination. Three patients (2.5 per cent) had hypercalcemia, and twenty-two (18 per cent) in whom renal function was not impaired had hyperphosphatemia. Increased alkaline phosphatase activity was found in 34 per cent of the patients tested. Hyperphosphatemia and increased alkaline phosphatase activity could not be correlated with other clinical or laboratory findings. Roentgenologic evidence of bone disease was found in eleven of twenty children examined, but in only ten of fifty-three adult patients.Seven cases of leukemia with hypercalcemia are reported. Six of the patients had acute leukemia; in the seventh case, however, the hypercalcemia was not related to the coexisting chronic lymphocytic leukemia. Symptoms of hypercalcemia preceded other evidence of acute leukemia in one case and in two reported previously. Early recognition of these cases is important since the hypercalcemia and its symptoms were reversed by corticosteroid therapy in all three instances. Roentgenologic evidence of bone disease was not always present at the time the hypercalcemia was discovered but usually appeared later. Serum phosphorus levels are usually normal or elevated in association with the hypercalcemia of leukemia, suggesting an osteolytic action other than that of parathyroid hormone. In one case of chronic lymphatic leukemia, hypercalcemia, hypophosphatemia and low tubular resorption of phosphate were corrected by removal of a parathyroid adenoma. In the first case, and in one reported previously, with hypercalcemia and hypophosphatemia, there was no evidence of parathyroid abnormality.

CHRONIC LYMPHATIC LEUKEMIA ASSOCIATED WITH LOCALIZED LYMPHOSARCOMA OF THE TERMINAL ILEUM, CECUM, AND APPENDIX. REPORT OF A CASE.

A case of chronic lymphatic leukemia and localized lymphosarcoma of the terminal ileum, cecum, and appendix is presented. In the light of current thinking the episode of trauma in this case is probably coincidental and has no etiological significance.