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Activated platelets may contribute to the metastatic behavior of tumor cells when the cancer cells and platelets interact. The interaction requires cell and platelet surface integrin. Thyroid hormone as L-thyroxine (T4) is the principal ligand for a hormone receptor on integrin αvβ3 on tumor cells and platelets. T4 activates the integrin, promoting platelet aggregation and degranulation (local ATP release) and stimulating tumor cell proliferation. By a variety of molecular mechanisms reviewed here, extracellular ATP promotes tumor cell invasiveness and metastasis and supports a role for T4 as a pro-metastatic factor.

Substantial clinical evidence indicates hyperthyroidism enhances coagulation and increases the risk of thrombosis. In vitro and clinical evidence implicate multiple mechanisms for this risk. Genomic actions of thyroid hormone as 3,5,3'-triiodo-L-thyronine (T 3 ) via a nuclear thyroid hormone receptor have been implicated, but recent evidence shows that nongenomic mechanisms initiated at the receptor for L-thyroxine (T 4 ) on platelet integrin αvβ3 are prothrombotic. The T 4 -initiated mechanisms involve platelet activation and, in addition, cellular production of cytokines and chemokines such as CX3CL1 with procoagulatory activities. These procoagulant actions of T 4 are particulary of note because within cells T4 is not seen to be functional, but to be only a prohormone for T 3 . Finally, it is also possible that thyroid hormone stimulates platelet-endothelial cell interaction involved in local thrombus generation. In this brief review, we survey mechanisms by which thyroid hormone is involved in coagulation and platelet functions. It is suggested that the threshold should be lowered for considering the possibility that clinically significant clotting may complicate hyperthyroidism. The value of routine measurement of partial thromboplastin time or circulating D-dimer in patients with hyperthyroid or in patients treated with thyrotropin-suppressing dosage of T 4 requires clinical testing.

Clinical Practice Points . Plasmablastic lymphoma (PBL) is a rare and highly aggressive variant of diffuse large B cell lymphoma with median survival of advanced stage patients varying between 6 and 15 months in previous reports. We report here a human immunodeficiency virus-infected patient surviving over 12 years following treatment for advanced PBL with EPOCH chemotherapy and intrathecal therapy. This case highlights the potential for improved survival in PBL with intensive chemotherapy. Further, literature review suggests promising prospects utilizing novel targeted therapies to increase the rate of prolonged responses.

Monoclonal gammopathy of undetermined significance (MGUS), the precursor to multiple myeloma, is more common in blacks than whites. The serum free light chain (sFLC) assay is an important prognostic test in MGUS, but no study has evaluated sFLC levels and ratios in black MGUS patients. One-hundred and twenty-five black MGUS patients at two urban centers were compared to the white population of the Mayo Clinic. The median age for blacks was 73 years [41-94] and 75% were male. The M-protein isotype in blacks was 81% IgG, 13% IgA, 2% IgM, and 4% biclonal compared to 70%, 12%, 16%, and 2%, respectively, in whites, (P < 0.0005). The median M-protein concentration for blacks was 0.44 gm/dL (trace-2.33) compared to 1.2 gm/dl in whites. An abnormal sFLC ratio was present in 45% of black compared to 33% of white (P = 0.01) patients. Using the Mayo Clinic risk model, black patients had a significantly lower proportion of higher risk MGUS compared to whites: low 43%, low-intermediate 45%, high-intermediate 10%, and high 2% (P = 0.014). Black patients with MGUS have significantly different laboratory findings compared to whites. The biologic basis for these disparities and their effect on prognostic assessment is unknown. Prognostic models based on these biomarkers should be used cautiously in nonwhite populations., (Copyright © 2011 Wiley-Liss, Inc.)

Splenic marginal zone lymphoma (SMZL) is an uncommon indolent B-cell lymphoma causing marked splenic enlargement with CD20-rich lymphoma cells infiltrating blood and bone marrow. In the pre-rituximab era, the treatment of choice for patients with symptomatic splenomegaly or threatening cytopenia was splenectomy, since chemotherapy had limited efficacy. Responses to splenectomy occurred in approximately 90% of patients. However, SMZL patients are often elderly and poor surgical risks. Since approval of rituximab, treatment of such patients with the anti-CD20 antibody both alone or in combination with chemotherapy has shown remarkable responses. In retrospective series of rituximab monotherapy totaling 52 patients, including both chemotherapy-naive and -refractory patients, overall responses of 88% to 100% were noted with marked and prompt regression of splenomegaly and improvement of cytopenias. Sustained responses occurred both with and without rituximab maintenance in 60% to 88% of patients at 3 years. Relapsed patients responded to second courses of rituximab monotherapy. Overall survival was comparable to that reported following splenectomy. Rituximab in combination with purine nucleosides may provide further improvement in progression-free survival; however, confirmatory prospective trials are necessary. These results suggest that splenectomy should no longer be considered as initial therapy for SMZL but rather as palliative therapy for patients not responsive to immunotherapy with or without chemotherapy.

Amyloidosis complicating multiple myeloma is an uncommon but well-recognized phenomenon. Multiple bone amyloidomas are rare as the initial presenting feature of myeloma. Solitary bone amyloidomas share common features with those of patients who have solitary plasmacytomas and progression to disseminated myeloma is common. We report a case of an elderly man who presented with extensive amyloid deposition in multiple plasmacytoma sites as well as evidence of amyloid in a fat pad aspirate but with none of the usual organ damage associated with systemic amyloidosis. This presentation is similar to a subset of patients said to have macrofocal myeloma. These patients are typically aged < 40 years, have no bone marrow involvement, and have a good prognosis. This report may represent the first description of macrofocal myeloma associated with amyloid deposition in an older individual.

Previous descriptions of familial myeloma have been mainly of Caucasian families. We report here eight African American families with familial multiple myeloma and monoclonal gammopathy identified over a 30 year period. Six patients with multiple myeloma (MM) and two with monoclonal gammopathy of unknown significance (MGUS) reported a family history of MM or had family members with MGUS found on screening. A pedigree compiled for each family included a history of other cancers. In the eight families, 21 of 58 first degree relatives had a plasma cell dyscrasia including 12 MM, eight MGUS, and one amyloidosis patient(s). The age of the MM patients ranged from 50 to 78 years (median 61 years). Four families had two members with MM, including one mother-son and three sibling pairs. Two MM families each had two additional first degree relatives with MGUS, with three generations involved in one family. Anticipation was suggested in two families with parent-child pairs with monoclonal gammopathy. The eight pedigrees had 66 members, 21 of whom had a diagnosis of cancer, including non-Hodgkin lymphoma and Hodgkin disease, or a clonal myeloproliferative disorder other than MM. Although the mode of genetic transmission and anticipation cannot be confirmed due to the small sample size, the increased number of MM and MGUS family members suggests underlying genetic susceptibility factors for plasma cell dyscrasias and possibly for other cancers in these families.

We previously reported durable complete responses following brief courses of rituximab and prednisone with or without cyclophosphamide in four patients with autoimmune haemophilia and inhibitor titres of 5-60 BU. We report here responses to this monoclonal anti-CD20 antibody in four additional patients, including two patients with inhibitor titres >200 BU. Factor VIII levels became normal 2-35weeks after 4 or 8 weekly doses of rituximab, brief courses of prednisone and in one patient immunoglobulin. Complete responses are ongoing at 10 months in two patients. Two patients relapsed: a patient whose initial inhibitor titre was 525 BU relapsed at 3.5 months and a long-term prednisone-dependent patient at 8.5 months. Both responded to second courses of rituximab and prednisone and are in remission. Our experience suggests that rituximab is a safe and effective addition to immunosuppression with prednisone and cyclophosphamide to treat autoimmune haemophilia, and may permit early discontinuation or even avoidance of these potentially toxic agents. High-titre inhibitor patients, however, may require multiple courses of rituximab or the addition of cyclophosphamide. Pending randomized studies, we propose an algorithm based on our experience and other reports for incorporating rituximab in the treatment of this rare disorder.

Plasma exchange is the standard treatment for thrombotic thrombocytopenic purpura (TTP). For patients refractory to plasma exchange, treatment options are limited and often unsuccessful. The platelet thrombi that form in acquired TTP are believed to result from the presence of procoagulant ultralarge multimers of von Willebrand factor (VWF) in the circulation due to autoantibody inhibition of VWF cleaving protease (ADAMTS-13), the enzyme that normally cleaves the ultralarge multimers. Rituximab, a chimeric monoclonal antibody against CD20, has been recognized as a useful therapy for antibody-mediated autoimmune disease. We therefore treated four patients with recurrent TTP with 2 or 4 weekly doses of rituximab in addition to corticosteroids, vincristine, plasma, or continuing plasma exchange. Three patients responded with prompt improvement in microangiopathic hemolytic anemia and thrombocytopenia, which allowed plasma exchange to be discontinued or avoided and prednisone to be rapidly discontinued. Two of the 3 responders have remained in unmaintained complete remission for 13+ months. The third patient relapsed at 13 months; a second course of rituximab and prednisone resulted in an unmaintained remission for 6+ months. All four patients were tested for ADAMTS-13 activity and its inhibitor at a point in their course when samples were available. Low ADAMTS-13 activity was noted in 3 patients tested at relapse, and the inhibitor activity was detectable in 2 patients. ADAMTS-13 activity increased during remission in one of these 2 patients although the patient had a persistence of the inhibitor. One patient tested only during remission had a normal ADAMTS-13 level. We conclude that rituximab may have a role and deserves further study in the treatment of patients with relapsing TTP., (Copyright 2004 Wiley-Liss, Inc.)

Autoantibodies against factor VIII (FVIII) are rare but can cause life-threatening bleeding requiring costly factor replacement and prolonged immunosuppression. We report 4 consecutively treated patients whose acquired FVIII inhibitors responded rapidly to immunosuppressive regimens that included rituximab, a monoclonal antibody against CD20(+) B cells. Three patients had spontaneously occurring inhibitors. The fourth, a patient with mild hemophilia A, developed both an autoantibody and an alloantibody following recombinant FVIII treatment. Pretreatment FVIII activities ranged from less than 1% to 4% and inhibitor titers from 5 to 60 Bethesda units (BU). One patient with polymyalgia rheumatica who developed the inhibitor while receiving prednisone responded to single agent rituximab. The hemophilia patient had rapid resolution of the autoantibody, whereas the alloantibody persisted for months. Responses continue off treatment from more than 7 to more than 12 months. This report adds to the growing evidence that rituximab has efficacy in immune disorders resulting from autoantibody formation.

Multicentric Castleman's disease is an atypical lymphoproliferative disorder for which multiple chemotherapeutic regimens have been used without much success. Role of biological response modifiers like interferon used as a single agent is discussed in this case report.

Recognizing that skilled history-taking is in danger of becoming a lost art, the American Board of Internal Medicine calls attention to the urgent need for internal medicine residency programs to ensure that these skills are taught and assessed. Although the Board's certification examination contains standardized items that test the physician's ability to use information from a patient's medical history, the written examination cannot assess the physician's ability to elicit that history. The Board believes that history-taking skills will become even more crucial as health care delivery changes, requiring more cost efficiency without sacrificing quality. By highlighting the skills of effective history-taking and strategies for assessment, the Board offers specific recommendations for its promotion as a key element of quality patient care.

Purpose: To report African Americans with primary iron overload diagnosed during life and to study iron stores in African Americans undergoing autopsy., Patients and Methods: We summarized information for 4 African-American patients diagnosed during life with iron overload not explainable by alcohol, blood transfusions, or ineffective erythropoiesis. We reviewed liver specimens and hospital records of 326 unselected adult African Americans who were autopsied, assessing Prussian blue-stained sections for hepatocellular iron and measuring iron quantitatively in specimens that stained positively. We calculated the hepatic iron index (the hepatic iron concentration in mumol/g dry weight divided by the age in years). In autopsy subjects we corrected the index to account for iron administered by blood transfusion (the adjusted hepatic iron index). The hepatic iron index is useful for distinguishing primary iron overload from the moderate siderosis that may accompany alcoholic liver disease. The normal index is < or = 1.0. An index > or = 1.7 cannot be explained by alcohol effects and an index > or = 1.9 indicates the magnitude of iron-loading found in Caucasian homozygous HLA-linked hemochromatosis., Results: The 4 living patients, all males and 27 to 50 years of age, had elevated body iron burdens and one or more of the following: hepatomegaly, cirrhosis, cardiomyopathy, diabetes mellitus, and impotence. Hepatic iron indices were 2.3, 11.5, and 20.2 in the 3 whose liver iron concentrations were measured. Among the autopsy subjects, 4 (1.2%), 2 men and 2 women aged 50 to 63 years, had adjusted hepatic iron indices > or = 1.9 (range 1.9 to 5.6)., Conclusions: Primary iron overload occurs in African Americans. Further studies are needed to define prevalence, pathophysiology and clinical consequences. Clinicians should look for this condition.

Purpose: This phase II study was undertaken to assess the efficacy and toxicity of the addition of continuous low-dose interferon alfa-2a (IFN) to fludarabine in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS)., Patients and Methods: Thirty-five patients were treated with fludarabine 25 mg/m2 intravenously (IV) on days 1 to 5 every 28 days along with IFN 5 x 10(6) U/m2 subcutaneously three times per week continuously for up to eight cycles. IFN doses were escalated to 7.5 x 10(6)/m2 at day 29 if constitutional toxicities were less than grade 3. Twenty-one patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), and 10 of these had received prior deoxycoformycin (pentostatin; DCF) and intermittent high-dose IFN; seven had received only topical therapies, and seven were untreated., Results: Four patients achieved a complete response (CR) and 14 achieved a partial response (PR) for an overall response rate of 51% (95% confidence interval, 35% to 70%). Four of 11 patients with visceral involvement responded. The median progression-free survival duration of the patients who responded was 5.9 months, and three of the complete responders are in unmaintained response after 18 to 35 months. Grade 3 or 4 hematologic toxicity occurred in 21 patients, including two who developed persistent bone marrow aplasia. Eighteen patients developed infections during therapy, including five with herpes zoster, one with Pneumocystis carinii, one with extrapulmonary tuberculosis, and two with disseminated toxoplasmosis., Conclusion: The combination of fludarabine with continuous low-dose IFN is an active regimen in patients with advanced MF/SS, including patients with visceral involvement and patients who progressed after prior therapy with DCF and IFN. This regimen has induced unmaintained remissions in a small subset of patients.

Purpose: This phase II study was undertaken to assess the efficacy and toxicity of alternating administration of pentostatin (deoxycoformycin [DCF]) and interferon alfa-2a (IFN) in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS)., Patients and Methods: Forty-one patients underwent therapy with alternating cycles of DCF 4 mg/m2 intravenously (IV) days 1 through 3 and IFN 10 million U/m2 intramuscularly (IM) day 22, and 50 million U/m2 intramuscularly (IM) days 23 through 26. Twenty-nine patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), six had not responded to topical therapies, and six had no previous treatment., Results: Two patients achieved a complete response (CR) and 15 achieved a partial response (PR), for an overall response rate of 41% (95% confidence interval, 26% to 58%). No responses were observed in the seven patients with visceral involvement. The median progression-free survival of patients who responded was 13.1 months. IFN-related constitutional symptoms were reported in 39% of patients; severe toxicities included cardiomyopathy in one patient, acute and chronic pulmonary dysfunction in four, and reversible mental status changes in two. Seven patients developed herpes zoster during therapy and six had staphylococcal bacteremia., Conclusion: These results suggest that the combination of DCF and IFN is an active regimen in MF patients without visceral involvement.

A 56-year-old African-American man presented with fever of unknown origin and peripheral blood and bone marrow findings of myelodysplastic syndrome (MDS): refractory anemia with an excess of blasts in transformation that subsequently progressed to acute myeloblastic leukemia (AML). Ultrastructural study of two bone marrow specimens having the findings of MDS revealed frequent, large tubuloreticular structures (TRS) in lymphocytes, plasma cells, macrophages, and endothelial cells. Several cylindrical confronting cisternae (CCC) were present in macrophages and an endothelial cell. Two partially developed CCC were present in a plasma cell. TRS and CCC were not observed in eight subsequent bone marrow specimens obtained during the 9-month course of the AML. This is the first reported occurrence of TRS and CCC in MDS. These inclusions are probably related to an unidentified viral infection or possibly to cytokines released by the dysplastic hematopoietic cells.

A patient presenting with marked inflammatory lymphadenitis and Jaccoud's arthritis was found to have a rearranged gene for the beta-chain of the T-cell receptor (TCR-beta) antigen in the lymph node DNA digests and normal germ line DNA in the peripheral blood lymphocytes. Four months later, the patient was diagnosed to have poorly differentiated adenocarcinoma of the lung with small foci of metastatic tumor in lymph nodes that contained the same extensive lymphocytic and inflammatory cell infiltrates noted earlier. Rearranged TCR-beta chain genes were detected in both lymph node and peripheral blood lymphocyte DNA at this time. The most likely explanation for the florid lymph node reaction and the unusual arthropathy appears to be a paraneoplastic immune response. The rearranged TCR-beta genes indicate a clonal T-cell expansion that most likely resulted from the aberrant immunologic response to the lung cancer.

Dual-parameter flow cytometric analysis of B-cell antigens and DNA content was used to determine the phenotypes of proliferating tumor cells (S-phase cells) from 30 patients with multiple myeloma. B4 (CD19), J5 (CALLA, CD10), B1 (CD20), and monotypic surface immunoglobulin (Slg) were expressed heterogeneously in 24 patients. J5 and monotypic Slg were found most frequently but were always expressed on a significantly lower percentage of cells than the antigens typically associated with plasma cells, cytoplasmic immunoglobulin (Clg) and T10 (CD38). S-phase cells were found in each antigen(+) subset. B antigen(+) cycling cells were demonstrated in 16 patients whose marrow or blood cells expressed B antigens exclusively in the hyperdiploid fraction and therefore were certainly part of the myeloma clone. Similar to the low level of proliferative activity of the T10(+), Clg(+), and PCA1(+) subsets, the percentages of cycling cells of the preplasma cell B-antigen-bearing myeloma subsets ranged from less than 1% to 12%. The tumor cells of four patients were also studied with dual-color surface antigen analysis and demonstrated independent expression of B antigens, with only rare coexpression of T10 and monotypic Slg, J5, or B4. These findings are consistent with the presence of distinct myeloma subsets bearing differing B phenotypes in the same tumor and provide evidence that the proliferation in myeloma is occurring at various developmental stages in the malignant B lineage. These antigens may be important targets for immunologic therapy aimed at eliminating the entire proliferating compartment of this B-cell tumor.

Two patients with myelofibrosis developed fever, leg pain and periostitis. The first patient had myelofibrosis with myeloid metaplasia and was symptomatic for months before x-rays showed periosteal new bone formation in the lower extremities. He subsequently developed periostitis of both upper extremities. Radiation of the lower extremities resulted in significant pain relief. The second patient had a past history of polycythemia vera and experienced painful periostitis of the tibiae and fibulae. 99mTechnetium pyrophosphate bone scans showed increased uptake in the involved bones in both patients. Asymptomatic or painful periostitis may be related to the increased bone blood flow associated with myelofibrosis. Radiation can afford successful palliation in the severely symptomatic patient.

The clinical course of three patients with cutaneous T-cell lymphoma (CTCL) in whom skeletal disease developed is presented and the literature on skeletal involvement in these disorders is reviewed. Three separate types of skeletal manifestations occurred: (1) osteolytic lesions, (2) osteoblastic lesions, and (3) diffuse osteoporosis. Hypercalcemia was present in two cases. Tumor cells from two patients in short-term culture secreted osteoclast-activating factor(s). Both of these patients had pathologic evidence of osteoclast activation in bone sections. Thus, the tumor cells in certain patients with CTCL may derive from a monoclonal proliferation of a T-cell subset capable of producing humoral bone-resorbing factor(s) similar to those demonstrated in cultures of mitogen- and antigen-activated normal lymphocytes. Since skeletal lesions are unusual, it would follow that other T-cell subsets account for pathologic cell proliferation in most patients with CTCL.

Mononuclear leukocytes (MNL) were isolated from human blood by Ficoll-Hypaque. These cells were further separated into lymphocyte (L) and monocyte (M) enriched fractions. L contained 99% lymphocytes and M contained 74% monocytes, a threefold enrichment over MNL. Specific binding to somatostatin, glucagon, and insulin was measured in the three fractions. Binding of all three hormones in the M fraction was increased by a factor of 3 compared with MNL and was linear with cell number. Binding of glucagon and insulin to the L fraction was very low while, in contrast, somatostatin binding was substantial and linear with lymphocyte number. Autoradiography confirmed the binding of glucagon to monocytes and of somatostatin to both monocytes and lymphocytes. Somatostatin is the first of the peptide hormones shown to bind to both types of circulating mononuclear cells, perhaps complicating quantification of somatostatin binding in disease states in which differential alteration of binding of lymphocytes or monocytes might occur.

To determine whether cytosine arabinoside (Ara-C) has a differentiating effect in vitro, marrow cells from nine patients with acute non-lymphocytic leukemia or myelodysplastic syndrome and eight non-leukemic controls were exposed to drug concentrations comparable to those achieved in vivo with low-dose Ara-C therapy. In soft agar cultures, the predominant effect of Ara-C at concentrations between 10(-8) M and 10(-6) M was cytotoxicity with a dose-dependent decrement in Colony Forming Unit of the granulocyte and monocyte lineage (CFUg/m) at 14 days. Growth in liquid cultures containing Giant Cell Tumor(GCT)-conditioned media without Ara-C resulted in a significant increment in the recovery of mature cells at day 10 from the non-leukemic cultures (P = 0.03), while only a minor increase was found in the leukemic cultures (P = 0.09). All liquid cultures exposed to greater than or equal to 10(-9) M Ara-C showed a marked reduction in the immature proliferating cell pool, with a concomitant increase in the percentage of mature non-dividing cells at 10 days. However, the absolute number of differentiated cells recovered remained constant or decreased in all non-leukemic and eight of nine leukemic cultures, compared with cultures without Ara-C. Enhanced recovery of differentiated cells was also never observed in any culture exposed to the relatively non-toxic 10(-9) M Ara-C. These in vitro findings support clinical observations suggesting that cytotoxicity rather than differentiation is the major mechanism involved in the therapeutic effect of low-dose Ara-C in acute leukemia and myelodysplasia.

Eight patients with small cell bronchogenic carcinoma treated with intensive combination chemotherapy, with and without radiotherapy, have been followed for a minimum of two and a half years without relapse. One patient, after a prodrome of macrocytic sideroblastic anemia, leukopenia, and thrombocytopenia, experienced erythroleukemia 34 months after starting chemotherapy, and cytogenetic studies revealed extensive chromosomal abnormalities. Another patient had persistent macrocytic anemia and pancytopenia two years after cessation of therapy. The remaining six patients had normal peripheral blood smears and cell counts. A significant incidence of preleukemia syndromes and acute leukemia appearing as late complications in intensively treated small cell lung cancer patients requires confirmation in larger series of long-term survivors. Prospective determination of marrow karyotype abnormalities may help to identify patients at greatest risk for developing secondary leukemia.

A prospective pretreatment staging evaluation was done on 49 consecutive patients with mycosis fungoides or the Sézary syndrome to study patterns of disease spread and prognostic factors. Routine staging procedures included complete blood count, blood chemistries, chest roentgenogram, lymphangiogram, radionuclide scans, bone marrow aspiration and biopsy, liver biopsy, and lymph node biopsy. Special evaluations included cytogenetic analysis, electron microscopy, and T-cell cytology. Extracutaneous lymphoma was documented by light microscopy in 51% of patients and by the three special procedures in 88%. Extracutaneous lymphoma was most frequent in blood and lymph nodes; 18% of patients had visceral involvement. Patients with generalized erythroderma had a higher frequency of extracutaneous disease than did patients with cutaneous plaques and tumors by both light microscopy and special studies. Survival was directly related to the type of skin involvement and the presence or absence of extracutaneous disease. Systemic dissemination of cutaneous T-cell lymphoma is frequent, generally asymptomatic, and develops early via the circulation. These findings may explain why cutaneous therapies are associated with a high frequency of relapse.

A 51-year-old man presented with a T-cell leukemia of large granular lymphocytes and rapidly developed a nephrotic syndrome due to presumptive minimal-change glomerulopathy. The E-rosette+, Ia+ cells demonstrated cytotoxic activity similar to that of natural killer lymphocytes but lacked other T-subset markers, except that one third of them bore Fc(IgG) receptors. Cytogenetic analysis revealed loss of chromosome 10 and the translocation (1;10)(p11;q11) in all metaphases. Regression of the leukemia after chemotherapy was accompanied by a dramatic resolution of the nephrotic syndrome, suggesting that the activated granular lymphocytes induced the renal lesion. The close association of a clonal T-lymphoproliferative disorder with minimal-change nephrotic syndrome lends further support to current views implicating activated T cells or their products in the pathogenesis of this glomerulopathy.