Biomedical subjects

K J Gajl-Peczalska

Publications and source records attributed to K J Gajl-Peczalska.

At least 19 recordsLinked to original sources

PubMed1994

Clinical characteristics of post-transplant lymphoproliferative disorders.

PURPOSE: To study the histopathologic findings, clinical course, and therapeutic outcome of patients who developed a lymphoproliferative disorder after undergoing solid organ transplantation. PATIENTS AND METHODS: A series of 26 patients who developed a lymphoproliferative disorder after solid organ transplant during a 27-year period were studied. RESULTS: The 26 patients ranged in age from 6 to 68 years (median 42 years). The lymphoproliferative disorder was diagnosed from 1 to 211 months (median 80 months) after transplantation. The type of transplant was kidney (n = 21), heart or heart-lung (n = 4), or liver (n = 1). Most patients received azathioprine and prednisone, in addition to antilymphocyte globulin or cyclosporine, for post-transplant immunosuppression. Eight patients had lymphoma that could be classified according to the International Working Formulation (IWF-F, IWF-G, IWF-H). Sixteen patients had polymorphic lymphoma, and 2 patients were classified as having polymorphic lymphoid hyperplasia. Patients were staged by the Ann Arbor staging system. Nine patients had stage I disease, 4 stage II, 6 stage III, and 7 stage IV. Central nervous system, lung, or marrow involvement was present in 27%, 23%, and 14% of patients, respectively. In the 17 patients studied, immunophenotype was monoclonal B-cell (n = 12), malignant T-cell (n = 2), or polyclonal B-cell (n = 3). The initial therapeutic approach was generally a reduction in immunosuppression, but, thereafter, the approach to therapy varied. In patients with localized disease, surgical excision and/or involved field radiotherapy were utilized as applicable. For patients with more extensive disease, other approaches such as high-dose acyclovir, combination chemotherapy, or alpha interferon were utilized. Overall, 15 of 26 patients (58%) responded to systemic therapy or were rendered disease-free either by surgery or radiation, including 8 (31%) with a complete remission (CR). Only 3 of 9 patients responded to chemotherapy, whereas 4 of 13 patients responded to acyclovir (including 3 patients who experienced CR). Remission duration ranged from 8 to 122 months (median 32+ months). Twenty-one of 26 patients (81%) have died. Survival ranged from less than 1 to 122 months (median 14 months). CONCLUSION: The outcome of patients with post-solid organ transplant lymphoproliferative disorders is poor, and the optimal approach to therapy is not clear. Newer therapeutic approaches are thus needed to improve the outcome of these patients.

Adolescent↗

PubMed1994

L3 acute lymphoblastic leukemia. Comparison with small noncleaved cell lymphoma involving the bone marrow.

The relationship between acute lymphoblastic leukemia (ALL-L3) and stage IV small noncleaved cell lymphoma with bone marrow involvement (SNCL) was analyzed by retrospective study of 45 patients. Twelve patients with ALL-L3 had tumour restricted to the marrow and blood with no evidence of an extramedullary tumor at their initial presentation. Nineteen patients with stage IV SNCL had evidence of extramedullary disease in addition to marrow and blood involvement. Fourteen patients with marrow and blood involvement by SNCL at the time of a first or second relapse were also studied. The median age of the ALL-L3 patients was 33.5 years, compared with 13 years for the patients with stage IV SNCL and 10.5 years for the marrow relapse patients. All of the ALL-L3 patients wre male; the male:female ratio for the SNCL patients was 17:2; for the relapse group, 9:5. The majority of the ALL-L3 patients had symptoms related to bone marrow failure; the majority of the SNCL patients had symptoms related to a tumor mass. Laboratory values at the time of initial diagnosis were similar for the ALL-L3 and SNCL patients, except that the median platelet count was lower in the ALL-L3 group. Despite extensive marrow involvement by tumor in most patients, frankly leukemic blood pictures were uncommon. Light-chain-restricted surface immunoglobulin on tumor cells was a consistent finding in all cases tested; the findings were similar in the three groups. Cytogenetic data, available for 19 cases, showed no difference between cases with and without extramedullary disease. The median survival was 5.1 months for ALL-L3 patients and 3.2 months for SNCL patients. The median survival from the time of bone marrow relapse was 2.3 months. These observations suggest that ALL-L3 and SNCL represent different manifestations of the same disease process.

Adolescent↗

PubMed1994

Late-developing Philadelphia chromosomes in a case of T-cell acute lymphoblastic leukemia.

A child with T-cell acute lymphoblastic leukemia (ALL) is presented who at relapse acquired two Philadelphia chromosomes (Ph). Molecular studies at relapse revealed a rearrangement of the major breakpoint cluster region (M-bcr) on chromosome 22. No rearrangements of the immunoglobulin heavy chain or T-cell beta receptor gene loci were demonstrated. This case supports the hypothesis that leukemogenesis in Ph-positive malignancies is a multi-step process, the first step of which may not necessarily involve acquisition of the Ph.

Child↗

PubMed1993

Lymphoproliferative process with natural killer cell phenotype. Histopathologic, ultrastructural, and surface marker observations.

We describe the clinical, structural, and immunophenotypic characteristics of a lymphoproliferative process characterized by persistent thrombocytopenia and prominent involvement of the spleen and, to a lesser degree, the liver. The proliferating cells lacked cytoplasmic azurophilic granules by light microscopy and on ultrastructural examination displayed prominent interdigitating cell processes and did not contain parallel tubular arrays. Immunophenotypically, the cells displayed markers of true natural killer cells (positive CD2, CD56, CD45, CD7, CD16, and CD33). No involvement of peripheral blood or bone marrow was detected. This case represents a proliferation of true natural killer cells probably arising in the spleen. The relationship of this process to other lymphoid proliferations at different sites with true natural killer cell or natural killer-like activity is unknown.

Adult↗

PubMed1992

Hyperplasia of type II pneumocytes in acute lung injury. Cytologic findings of sequential bronchoalveolar lavage.

The organizing stage of acute lung injury syndrome is characterized, in part, by a reactive hyperplasia of type II pneumocytes. These cells may be recovered in large numbers and in an excellent state of preservation by bronchoalveolar lavage. It was noted recently that such cells in lavage samples may mimic adenocarcinoma. To examine the dynamics of type II pneumocyte shedding in acute lung injury, we studied 62 bronchoalveolar lavage samples from 38 patients with acute onset of the adult respiratory distress syndrome (median age, 54 years). A single lavage was performed in 25 patients, whereas from two to five studies were performed in 13 individuals. The timing of lavage ranged from 1 to 435 days after the onset of respiratory distress. Type II pneumocytes were present in 12 specimens as follows: 6 of 24 (25%) samples from days 1 to 3, 4 of 9 (44%) samples from days 4 to 10, and 2 of 11 (18%) samples from days 21 to 32. Specimens obtained after day 32 never contained such cells. Cytologically, type II pneumocytes may resemble the cells of acute radiation injury. Alternatively, they may be smaller, with an increased nuclear-cytoplasmic ratio, nuclear membrane irregularities, and prominent nucleoli, thus resembling the cells of adenocarcinoma. They may shed singly or in groups. A spectrum of changes from small cells to large, fully hyperplastic type II cells may be seen. Recognition of the morphologic features of type II pneumocytes and careful clinical correlation usually will suffice to prevent a false diagnosis of malignancy. Sequential lavage provides a means to study pulmonary epithelial changes after lung injury.

Acute Disease↗

PubMed1991

B-cell lymphoproliferative disorders after bone marrow transplant. An analysis of ten cases with emphasis on Epstein-Barr virus detection by in situ hybridization.

Ten patients with B-cell lymphoproliferative disorders (BLPD) after bone marrow transplant were studied in a retrospective analysis of 81 specimens available from biopsy and autopsy material. Histologic review, immunophenotyping, and in situ hybridization (ISH) for Epstein-Barr virus (EBV) sequences were done. Sixty-four specimens showed morphologic evidence of BLPD, demonstrating a heterogeneous spectrum with various degrees of plasmacytoid differentiation. Immunophenotypic evidence of clonality was found in six patients. The ISH detected EBV sequences in all ten patients, including 60 of the 64 specimens with morphologic evidence of BLPD. In addition, ISH identified EBV-infected lymphoid cells in two of 17 sites without morphologic evidence of BLPD. These data demonstrate the utility of ISH for detecting EBV genome in this setting and provide further evidence for the etiologic role of EBV in the pathogenesis of BLPD.

Adolescent↗

PubMed1991

Transformation of chronic lymphocytic leukemia to small non-cleaved cell lymphoma: a cytogenetic, immunological, and molecular study.

A patient with chronic lymphocytic leukemia (CLL) transforming into a small non-cleaved cell lymphoma (SNCL) with the occurrence of a t(8;22) is described. The SNCL and the CLL were both found to have a germline lambda light chain gene configuration and the same heavy chain and kappa light chain gene rearrangements. The SNCL was CD10 (CALLA) negative and appeared to be CD5 negative. It is concluded that the SNCL is derived from the CLL and that activation of the c-myc oncogene may have played a role in this transformation.

Bone Marrow↗

PubMed1990

Immunoblastic lymphoma of T-cell type in a chronically immunosuppressed renal transplant recipient.

A case of non-Hodgkin's lymphoma of T-cell type occurring in a renal transplant recipient is described. This lymphoma was classified as large cell, immunoblastic type and presented as a mediastinal mass, although it was demonstrated to be disseminated at autopsy two weeks later. Lymphoma cells expressed the immunologic profile of a mature, activated cytotoxic/suppressor T-lymphocyte. T-cell receptor gene rearrangement and karyotypic studies confirmed a clonal T-cell genotype. Molecular studies failed to demonstrate any association with Epstein-Barr virus or human T-cell lymphotropic virus type I or type II. Pathogenesis of lymphomas in this clinical setting is discussed.

Adult↗

PubMed1990

Epstein-Barr virus--determined clonality in posttransplant lymphoproliferative disease.

Analysis of the genomic termini of Epstein-Barr virus can provide valuable insight into the cofactor role of EBV in the development of B cell lymphomas and lymphoproliferative disease. We report EBV genomic findings in pathologic specimens from 10 patients who developed lymphoma or lymphoproliferative disease after renal or bone marrow transplantation. Endonuclease restriction patterns of EBV genomic termini are highly variable in size in both the episomal and linear configuration. This variability in fragment size permits direct assessment of tissue clonality in EBV-infected material. Hybridization with terminus-specific probes also reveals configuration of viral genome (circular and latent vs. linear and replicative). Nine of 10 patients had tumors with mono- or biclonal episomal markers, and 4 of 10 had evidence of linear or replicative virus. Analyses of virally determined markers were compared to immunoglobulin gene rearrangement studies, histologic immunophenotyping, cytogenetics, and clinical outcome. These 10 cases represent a spectrum of lymphoproliferative disorders ranging from benign polyclonal to malignant monoclonal disease. The molecular data lend credence to two important aspects of viral pathogenesis: (1) the finding of a homogeneous episomal population in the monoclonal tumors suggests that EBV infection is an early event in tumorigenesis that occurs before clonal expansion; and (2) therapeutic efficacy of acyclovir has been shown only in presence of polyclonal disease but may impact on intermediate stages where linear replicative virus can be found. Finally, the various assessments of tumor clonality were compared, and although heterogeneity was seen among patients and among diagnostic methods, analyses at the molecular level using virus and immunoglobulin gene specific probes were concurrent and provide the more sensitive means for detection of clonality.

Adolescent↗

PubMed1990

Oligoclonal T cell receptor gene rearrangements in blood lymphocytes of patients with acute Epstein-Barr virus-induced infectious mononucleosis.

Gene rearrangement studies were performed on blood lymphocytes from eight patients with acute Epstein-Barr virus-induced infectious mononucleosis. The diagnosis in each case was based on characteristic clinical, hematologic, and serologic findings. The blood lymphocytes in each patient consisted predominantly of CD8+ T cells. EBV DNA was detected in seven patients by Southern blot analysis (EBV Bam HI W probe, Bam HI). A germline configuration was found for the immunoglobulin heavy and light chain genes (JH probe, Bam HI and Eco RI; C kappa probe, Bam HI; and C lambda probe, Eco RI). T cell receptor gene rearrangements were detected with J gamma and J beta 1 + 2 probes. Using a J gamma probe with two different restriction enzymes (Bgl II and Eco RI), the blood from each patient showed several bands corresponding to the polyclonal pattern previously described in the blood of normal individuals. Using J beta 1 + 2 probes with two different restriction enzymes (Bgl II and Bam HI), each case showed from 3 to about 12 extragermline bands of varying intensity and in different locations from case to case. In addition, each case showed relative deletion of the J beta 1 germline band. This oligoclonal pattern of T cell receptor gene rearrangements has not been previously reported in benign or malignant T cell populations.

Acute Disease↗

PubMed1989

Confirmation of the heterogeneity of posttransplant Epstein-Barr virus-associated B cell proliferations by immunoglobulin gene rearrangement analyses.

Immunoglobulin gene rearrangement analysis is a sensitive method for determining clonality of B cell proliferations. We have examined tissue obtained from five renal and one cardiac allograft recipient with Epstein-Barr virus-associated B cell proliferations for immunoglobulin gene rearrangements. Biopsies from two patients with lesions that were hyperplastic morphologically, polyclonal by cellular immunoglobulin staining, and had diploid karyotypes, had no detectable gene rearrangements and were, therefore, consistent with benign reactive processes. These patients are alive without evidence of disease 37 and 57 months after diagnosis. In a biopsy from one patient with a lesion that was malignant lymphoma morphologically, monoclonal by cellular immunoglobulin staining, and had clonal cytogenetic abnormalities, clonal gene rearrangements were detected in a majority of cells, confirming their neoplastic nature. In biopsies from an intermediate group of three patients with morphologically malignant proliferations that were composed predominantly of a polyclonal population of B cells, clonal gene rearrangements were also found, consistent with early malignant transformation in a subpopulation of cells. These findings confirm the heterogeneity of the posttransplant EBV-associated lymphoproliferative diseases and have significant implications for our understanding of the pathogenesis of EBV-induced infections and related lymphomas.

Adolescent↗

PubMed1989

True histiocytic lymphoma: histopathologic, immunophenotypic and genotypic analysis.

Five cases of true histiocytic lymphoma (THL) were analysed by immunophenotyping and immunoglobulin/T-cell receptor genotyping. These cases showed striking morphologic diversity but a strong degree of immunophenotypic homogeneity. The malignant cells reacted with multiple histiocytic markers including CD11c (Ki-M1, LeuM5), CD14, CD68 (Ki-M6) and Ki-M8; anti-HLA-DR and non-specific esterase staining was also found in all cases. The malignant cells did not express monoclonal immunoglobulin and did not react with the B- or T-cell monoclonal antibodies used except for those known to be cytoplasmically expressed in monocytes/histiocytes, such as CD4 and CD19; B- and T-cell staining was otherwise limited to background small lymphocytes. By genotypic analysis, three cases showed rearrangements: one with T beta, one with T beta and immunoglobulin heavy chain (JH) and one with both JH and light chain; the remaining two cases retained their immunoglobulin and T-cell receptor genes in germline configuration. The results not only suggest that certain subsets of the histiocyte/reticulum cell system may be capable of rearranging immunoglobulin or T beta genes while simultaneously expressing multiple histiocytic surface antigens but also demonstrate the necessity of using multiple histiocytic-specific monoclonal antibodies and cytochemical staining in diagnosing THL. Gene rearrangement studies must be interpreted in conjunction with immunophenotyping and morphology in the determination of cell lineage.

Adolescent↗

PubMed1989

Four new recurring translocations in non-Hodgkin lymphoma.

The identification of recurring chromosomal translocations has provided clues to the gene regions important in lymphoma development. Among 157 patients with non-Hodgkin lymphoma studied by cytogenetic analysis, four new recurring translocations have been identified--t(8;9) (q24;p13), t(11;18)(q21;q21), t(14,15)(q32;q15), and an unbalanced translocation giving rise to der(22)t(17;22) (q11;p11). Each translocation appeared twice. The t(11;18) was the only karyotypic abnormality in the two patients with it, and the t(14;15) was the sole karyotypic abnormality in one patient. All translocations were found in B-cell malignancies and were associated with both nodal and extranodal disease. Among the regions affected, only the immunoglobulin heavy-chain gene MYC, and BCL2, have thus far been associated with lymphoma. The breakpoint sites identified by these translocations warrant further investigation at the molecular level.

Aged↗

PubMed1989

Immunophenotype-karyotype associations in human acute lymphoblastic leukemia.

The present study is a detailed analysis of the cytogenetic features of leukemic cells from 104 immunologically classified acute lymphoblastic leukemia (ALL) (78 B lineage and 26 T lineage) cases. Clonal chromosomal abnormalities were found in marrow blasts from 77 of 104 (74%) cases. Hyperdiploidy was much more frequent in B-lineage ALL cases, whereas normal diploidy was more common in T-lineage ALL cases. Fifty-nine of 104 cases (46 of 78 B-lineage ALL and 13 of 26 T-lineage ALL cases) had structural chromosomal abnormalities. Structural abnormalities involving 2p11, 7p13, 7p22, proximal q arm of 7 (7q11 or 7q22), 11q23-24, and translocations involving 12p11-13 appeared to be B-lineage specific. By comparison, structural abnormalities involving 7p15, 7q32, and 14q11 displayed T-lineage specificity. Structural abnormalities involving 9p22-p23 or 14q32, del (6)(q21-q23), del (12)(p11-p13), and the Philadelphia chromosome were found in B-lineage as well as T-lineage ALL cases. This study expands the current knowledge about immunophenotype-karyotype associations in ALL.

Adolescent↗

PubMed1988

Use of colony assays and anti-T cell immunotoxins to elucidate the immunobiologic features of leukemic progenitor cells in T-lineage acute lymphoblastic leukemia.

The specific binding of radioiodinated rIL-2 to fresh marrow blasts from T-lineage acute lymphoblastic leukemia (ALL) patients was initially investigated. The estimated number of radioiodinated rIL-2 molecules bound per blast ranged from undetectable to 1948. In colony assays, 72% of 32 cases analyzed showed a significant proliferative response to rIL-2, which depended on PHA-stimulated lymphocyte conditioned medium activation. Colony stimulation indices correlated with the number of radioiodinated rIL-2 molecules bound per blast but not with expression of CD25/Tac Ag on fresh marrow blasts or primary colony blasts. These findings provide evidence that in T-lineage ALL functional IL-2R proteins are expressed on leukemic progenitor blasts which may be distinct from Tac Ag. We used the mAb 35.1, T101, and G3.7 to test for expression of CD2, CD5, and CD7 on fresh marrow blasts from 126 T-lineage ALL patients. CD2, CD5, and CD7 were expressed in 84%, 93%, and 99% of cases, respectively. Furthermore, colony blasts that represent the early progeny of leukemic progenitor blasts were also CD2+CD5+CD7+. Ricin conjugates of 35.1, T101, and G3.7 mAb were used as Ag-specific cytotoxic probes to test for expression of CD2, CD5, and CD7 at the level of T-lineage leukemic progenitor blasts. Each immunotoxin was able to selectively eliminate greater than 99% of leukemic progenitor blasts, providing unique and direct evidence that these cells co-express CD2, CD5, and CD7. Neither mixtures of anti-CD5 and anti-CD7 nor anti-CD2, anti-CD5, and anti-CD7 immunotoxins were more effective against blast progenitor cells than the individual immunotoxins alone, confirming that CD2, CD5, and CD7 are not expressed on non-overlapping progenitor cell subpopulations.

Antibodies, Monoclonal↗

PubMed1988

Immunophenotyping of hematopoietic malignancies in paraffin sections.

Immunophenotyping of hematopoietic malignancies is usually accomplished in frozen sections or cell suspensions. To determine whether this procedure was also feasible in paraffin sections, we performed a double-blind immunoperoxidase study of 65 hematopoietic tumors whose phenotypes had been determined previously in fresh tissue. A selected antibody panel was used, including anti-LN2, UCHL-1, anti-cathepsin B, anti-Leu M1, anti-MB2, and anti-MT1. A correct phenotype was obtained on paraffin sections in 95% of cases. All 31 B-cell malignancies were properly classified, showing reactivity for LN2 and MB2. In 14 of 15 T-cell hematopoietic malignancies, all cells reacted with anti-MT1 and/or UCHL-1; the 1 case negative for these antigens was misdiagnosed as a B-cell tumor because of misinterpreted LN2 reactivity in benign histiocytes. Four of 5 true histiocytic neoplasms were positive for cathepsin B and LN2 but lacked other antigens; the fifth case was wrongly considered a B-cell proliferation because only bland histiocytes displayed cathepsin B. Only 1 of 7 Hodgkin's lymphomas was misdiagnosed (as a T-cell tumor); in the other 6 cases, Reed-Sternberg cells were reactive for LN2 and LEU M1. Five of 6 extramedullary myeloid leukemias also stained for LN2, MT1, and LEU M1. One showed LN2, MB2, and MT1; this case was classified as a B-cell neoplasm and indeed represented a pre-B-cell transformation of chronic myelogenous leukemia. These results show that the specified panel of antibodies may be useful for immunophenotyping of hematopoietic neoplasms when only paraffin sections are available for analysis. However, it cannot supplant traditional cell-marker studies of hematopoietic tumors because of its lesser accuracy.

Antibodies, Monoclonal↗

PubMed1988

Clonal rearrangement for immunoglobulin and T-cell receptor genes in systemic Castleman's disease. Association with Epstein-Barr virus.

Castleman's disease is a morphologically and clinically heterogeneous lymphoproliferative disorder. Both a localized benign variant and an aggressive form with systemic manifestations have been described. To investigate the differences between these variants of Castleman's disease, the authors analyzed lymph node DNA from 4 patients with the localized type and 4 with the systemic type of Castleman's disease for immunoglobulin and T-cell receptor gene rearrangements. The role of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) was also studied by viral genomic DNA probes. They detected clonal rearrangements in 3 of the 4 patients with the systemic variant of Castleman's; no patients with localized disease had rearrangements. Copies of EBV genome were also detected in 2 of the 3 patients with clonal rearrangements. These results suggest that systemic Castleman's disease is a disorder distinct from the classical localized variant in that it may evolve into a clonal lymphoproliferation.

Adolescent↗

PubMed1988

Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation.

B cell lymphoproliferative disorders (BLPD) developed in eight patients following bone marrow transplantation (BMT) for leukemia (five patients) or immunodeficiency (three patients). Recipients of T depleted marrow from a mismatched donor were at particularly high risk of this complication. Six of 25 (24%) recipients of mismatched T depleted bone marrow developed BLPD. In contrast, none of 47 matched T depleted transplants, one of ten (10%) who received non-depleted marrow from an unrelated donor, and only one of 424 matched non-depleted transplants were associated with BLPD. Epstein-Barr virus (EBV) specific serology and DNA hybridization studies demonstrating five to 50 copies of EBV genome/cell in involved tissues implicate this virus as an associated etiologic agent. Restriction fragment length polymorphism (RFLP) and cytogenetic analysis of involved tissue demonstrated donor origin (five of seven) or host origin (two of seven). Histologic appearance was similar to EBV-induced polymorphic B cell proliferations described following solid organ transplantation, or which occur de novo in primary immunodeficiency. Six of seven patients with adequate tissue available for study were found to have monoclonal proliferations by: in situ immunofluorescence (six of seven), and/or immunoglobulin gene rearrangement, (four of six). Cytogenetic analysis of involved tissues from four patients showed a normal karyotype, whereas two had multiple clonal chromosomal abnormalities. Seven patients died despite aggressive attempts at therapy with combinations of antiviral, immunologic, and chemotherapeutic agents.

Antibodies, Viral↗