Treatment and biology of lymphomatoid granulomatosis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8029-8029 ◽  
Author(s):  
B. R. Healey Bird ◽  
N. Grant ◽  
K. Dunleavy ◽  
J. Janik ◽  
J. Cohen ◽  
...  

8029 Background: LYG is a rare angiocentric-destructive process with EBV+ B-cells and reactive T-cells. LYG is graded with grades I-II showing rare-moderate large EBV+ B-cells (usually polyclonal or oligoclonal) and grade III showing numerous large EBV+ B-cells (usually monoclonal), likely reflecting progressive transformation. Historically, steroids and/or chemotherapy have a 14 mos median survival. Methods: We are investigating Interferon-a (I-a) for grade I/II and dose-adjusted EPOCH ±Rituximab (R) for grade III LYG. Results: Characteristics of 53 pts are: male sex 68%; median age (range) 46 (17–67) and median ECOG P.S. 1 (0–3). Disease sites include lung 98%, CNS 38%, kidney 15%, skin 17%, liver 19% and nodes 4%. On study LYG grades are I-30%, II-26% and III-44%. Prior treatment was none-28%, chemotherapy± R-34%, and steroids alone-40% of pts. For grades I/II, I-a is begun at 7.5 million IUs TIW and escalated as tolerated until disease regression and continued 1 yr after CR. Of 31 patients treated with I-a, PFS is 62% at the median f/u of 5.3 yrs. Of 25 evaluable pts (3 NE; 3 TE), 60% had sustained CR for a median of 60 mos (4–175). In 9 pts who progressed on I-a, grade III was found in 5. Thus, in 20 pts with only grade I/II, 75% had sustained CR with I-a. In 11 evaluable pts with CNS disease, 81% achieved remission with I-a alone. The median time to remission is 9 mos (3–40) and median I-a dose is 20 MIU (7–40). Among 24 pts receiving DA-EPOCH±R, PFS is 40% at the median f/u of 28 mos. Of 21 evaluable pts (2 NE, 1 TE), 66% achieved CR. OS of all 53 pts is 68% at the median f/u of 4 yrs. Median EBV viral loads in 29 pts at study entry were 18 copies/10e6 genome equivalents (0–22727) (normal<200). Lymphocyte subsets in 30 pts showed a median CD4–428 (24–2322) and CD8–165 cells/mm3 (42–1316). In 12 pts in CR and with serial values, the mean CD8 cells (131 ± 44) (p2= 0.013) but not CD4 cells (65 ± 75) increased with treatment. Conclusions: High dose I-a produces sustained remissions in grade I/II LYG and is effective in CNS LYG. DA-EPOCH±R can produce durable CRs in grade III LYG. We hypothesize LYG emerges in a compromised immune milieu and undergoes progressive transformation if not effectively treated. Historical results suggest steroids may allow transformation by compromising immune function. No significant financial relationships to disclose.

Author(s):  
M L Choong ◽  
S H Ton ◽  
S K Cheong

The lymphocyte subsets in the peripheral blood of healthy Malaysian adults (212 subjects, age 18–71 years) were analysed using a flow cytometer FACScan in an effort to establish a reference range for the lymphocyte subsets. The lymphocyte subsets studied were T cells (CD3), B cells (CD19), natural killer (NK) cells (CD3−CD16+/CD56+), helper/inducer cells (CD4), cytotoxic/suppressor cells (CD8) and the helper/suppressor ratio (CD4/CD8). The distributions of T cells, CD4 cells and CD8 cells were symmetric about their means while B cells, NK cells and CD4/CD8 ratio followed a skewed distribution. Differences in race were observed for T cells, NK cells, CD4 cells and CD4/CD8 ratio where the Indians were significantly different from the Malays and the Chinese (higher T cells, CD4 cells and CD4/CD8 ratio and lower NK cells). The B cells were significantly lower in the Chinese than the Malays and the Indians. Age differences were seen only in the Chinese where increased CD4 cells and CD4/CD8 ratio, and decreased CD8 cells were observed. A sex difference was observed only in the Chinese where the CD4/CD8 ratio was significantly higher in females than males.


Author(s):  
Johanna Waidhauser ◽  
Pia Nerlinger ◽  
Tim Tobias Arndt ◽  
Stefan Schiele ◽  
Florian Sommer ◽  
...  

Abstract Introduction Cellular immune response to cancer is known to be of great importance for tumor control. Moreover, solid tumors influence circulating lymphocytes, which has been shown for several types of cancer. In our prospective study we elucidate changes in lymphocyte subsets in patients with colorectal carcinoma compared to healthy volunteers. Methods Flow cytometry was performed at diagnosis of colon carcinoma to analyze B cells, T cells and NK cells including various subtypes of each group. Univariate and multivariate analyses including age, gender, tumor stage, sidedness and microsatellite instability status (MSI) were performed. Results Forty-seven patients and 50 healthy volunteers were included. Median age was 65 years in patients and 43 years in the control group. Univariate analysis revealed lower total lymphocyte counts, lower CD4 + cells, CD8 + cells, B cells and NKs including various of their subsets in patients. In multivariate analysis patients had inferior values of B cells, CD4 + cells and NK cells and various subsets, regardless of age and gender. Naïve, central memory and HLADR + CD8 + cells showed an increase in patients whereas all other altered subsets declined. MSI status had no influence on circulating lymphocytes except for higher effector memory CD8 + cells in MSI-high patients. Localization in the left hemicolon led to higher values of total cytotoxic T cells and various T cell subsets. Conclusion We found significant changes in circulating lymphocyte subsets in colon carcinoma patients, independent of physiological alterations due to gender or age. For some lymphocyte subsets significant differences according to tumor localization or MSI-status could be seen.


1998 ◽  
Vol 7 (3) ◽  
pp. 285-297 ◽  
Author(s):  
Douglas A. Coddington ◽  
Hua Yang ◽  
Geoffrey Rowden ◽  
Pat Colp ◽  
Thomas B. Issekutz ◽  
...  

Wistar Furth (RT1u) islets transplanted under the renal capsules of streptozotocin-diabetic Lewis (RT1l) rats reject after 5–6 days of normoglycemia. Hand-picked WF islets (1500–2000) were transplanted under the kidney capsules of diabetic Lew or WF rats. Rats bearing iso- or allografts were killed on posttransplant days 2, 4, and 6. Serial frozen sections of grafts and controls were stained by immunoperoxidase for rat MAC-1, class II MHC, CD2, CD4, CD8, B-cells, VLA-4, LFA-1, L-selectin, ICAM-1, and VCAM-1. Infiltrating cells, parenchymal cells, and endothelial cells in five distinct compartments (i.e., peritoneal reflection, subcapsular perivascular space, islet grafts, graft–kidney interface, and kidney) were evaluated for expression of the various markers at each interval. Significant infiltrates arrived in three distinct waves in both iso- and allografts. First, macrophages blanketed the peritoneal capsular reflection and infiltrated by day 2. Second, the first wave of lymphocytes arrived in the edematous subcapsular soft tissue via capsular vessels by day 2 (allo > iso). Third, the second wave of lymphocytes arrived from the renal parenchyma to form a dense band at the graft–kidney interface and around grafts by days 4 and 6 (allo >>> iso); CD4+ cells vastly outnumbered CD8+ cells, with CD4+ cells being mobilized first and from interstitial vessels throughout the entire kidney. CD8+ cells emigrated only from renal interstitial vessels adjacent to the graft. Large numbers of L-selectin+, VLA-4+, and LFA-1+ cells were seen in the infiltrates with the most intensely staining cells being intravascular. B-cells composed a very small proportion of infiltrating cells in both allo- and isografts. Endothelial staining for ICAM-1 and VCAM-1 was prominent throughout. Both class II MHC and ICAM-1 expression were induced on renal tubular epithelial cells, but neither was found on islet parenchymal cells. In conclusion, this study shows that islet allograft rejection is more complex than previously realized.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1265-1265
Author(s):  
Harry F Dean ◽  
Angelica Cazaly ◽  
Carol Hurlock ◽  
Anthony P Williams ◽  
Peter W Johnson ◽  
...  

Abstract Abstract 1265 The number of survivors who have undergone high-dose chemotherapy (HDT) with autologous progenitor cell rescue for malignant lymphoma is increasing. Data on long-term immunological reconstitution is limited, particularly for lymphocyte populations that are now more readily enumerated. Despite consensus guidelines, routine primary revaccination of this patient population has not been universally adopted. Methods From the Wessex Blood and Bone Marrow Transplant Registry, 130 patients (pts.) with malignant lymphoma, who had undergone HDT, and were known to be in an ongoing continuous remission for at least 3 years were identified and invited to participate with the aim of quantifying lymphocyte subsets and serological memory. Thirty-seven pts., median age 52 years (range 30–71) consented to study participation; their histologies comprised: diffuse large B-cell lymphoma, 32%; Hodgkin's disease, 27%; follicular lymphoma, 27%; other lymphomas, 14%. The median follow-up from the time of HDT to study entry was 10.6 years (range 3.0–20.2). All, except 4 pts., had received peripheral blood derived progenitor cells, which had been purged in 2 pts. An age matched population (median 56 years) of 14 healthy individuals (predominantly patient spouses) served as controls. Lymphocyte subsets in peripheral blood were assessed using multicolour flow cytometric analysis with a 16 antibody panel. Serum antibody levels to measles, mumps, rubella, HiB, tetanus and pneumococcus were determined by ELISA. Results There was no significant difference in T, B and NK-cell populations between long-term follow-up pts. and controls, however even at median follow-up of 10 years there were persisting altered CD4+/CD8+ ratios with a reduced proportion of CD4+ cells in pts. compared to controls (median CD4+ 43% vs. 63% respectively; P<0.001). Naïve CD4+ cells were profoundly reduced in patients (P<0.001) yet effector memory and central memory CD4+ cells were higher in the pts. (P<0.001 and P=0.009 respectively).The effector memory RA population (intermediate between naïve and effector T-cells) were found in similar proportions between pts. and controls. Within the CD8+ population, the naïve population was reduced (P<0.001) with a corresponding increase in CD8+ memory cells in pts (p<0.001) however there was no difference in the level of central and effector memory CD8+ cells between pts. and controls. CD4+ T-cell numbers positively correlated with time form transplant, showing a continuous linear relationship. There were no significant differences in the proportion of memory and naïve B-cells between pts. and controls. Similarly there was no difference in marginal zone-like, class switch subtyes and mature plasmablasts proportions between the two groups. Uptake of revaccination following HDT was sporadic. Despite only 15 pts. (and only 1 pt receiving full course) being revaccinated, all patients demonstrated tetanus antibody levels above the minimal protective level. In two pts. who had received only a single dose of tetanus vaccine had antibody levels only just above the minimum. No pts. had been revaccinated against measles, mumps or rubella: 58%, 43% and 23% of pts respectively were below the equivocal serological level for immunity. No pt. had received pre HDT HiB vaccination and only 1 post HDT; 11% were below the minimal protective level. Four pts. had been vaccination against pneumococcus pre HDT and 13 pts. post: In 33% pts. antibody levels were below the minimum protective level. Conclusions Even at a median of 10 years following curative HDT, defects in lymphocyte subsets persist. The sustained reduction in naïve T-cell subsets, likely as a result of thymic incapacity, resulted in a peripheral T-cell population with a restricted TCR repertoire and the potential for impaired responses to novel antigenic stimuli many years after HDT. Other lymphocyte lineages however were able to fully reconstitute. Lack of serologically determined immunity was common, and the risk of incomplete vaccination scheduling demonstrated. In line with consensus statements, pts. following HDT should undergo full course revaccination or at least have assessment of their serological memory quantified to minimise the risk of infectious morbidity. Disclosures: No relevant conflicts of interest to declare.


1996 ◽  
Vol 7 (4) ◽  
pp. 288-291 ◽  
Author(s):  
A Levin ◽  
G Brubaker ◽  
J S Shao ◽  
D Kumby ◽  
T R O'Brien ◽  
...  

With the FACSCount TM flow cytometer, counts of CD4, CD8 and CD3 lymphocytes and CD4/CD8 ratios were performed in a rural hospital in Tanzania. A total of 168 subjects (21 HIV-1 seropositive and 147 HIV-1 seronegative) were tested as part of a population-based serosurvey and AIDS education programme; 134 other subjects were hospitalized patients who had signs and symptoms suggestive of AIDS (69 HIV-1 seropositive and 65 HIV-seronegative). Mean values for the 147 HIV-1 seronegative subjects from the local population were 980 CD4 cells (95% CI 930, 1031), 598 CD8 cells (560, 635) and CD4/CD8 ratio 1.78 (1.68, 1.89). Seropositive subjects from the local population had significantly lower CD4 cell counts, higher CD8 counts and a lower CD4/CD8 ratio. CD4 cells were significantly lower and CD8 cells significantly higher in HIV-1 seropositive hospital patients compared to HIV-1 seronegative patients. However, 23 (35%) seronegative hospital patients had CD4 counts lower than 600. These results establish baseline values for the lymphocyte subsets in this population and indicate that this technique can be used in remote areas to monitor progress of HIV-infected individuals.


1998 ◽  
Vol 84 (4) ◽  
pp. 489-492 ◽  
Author(s):  
Massimo C. Barberis ◽  
Luca Vago ◽  
Giancarlo Cecchini ◽  
Manuela Bramerio ◽  
Giuseppe Banfi ◽  
...  

Aims and background The aim of this study was to compare the local immune response in two groups of patients with high-grade cervical intraepithelial squamous lesions (SIL): one with HIV infection and the other with HPV infection alone. Materials and methods 16 conization specimens (8 from HIV-infected and 8 from non-HIV-infected patients) of HPV-related, high-grade SIL were selected. The specimens from non-HIV patients were considered as controls. The total number of Langerhans cells, CD4 and CD8 cells present in 10 field areas (3.120 mm2) was recorded in each case. In HIV patients CD4 and CD8 peripheral counts were performed immediately before surgery. Results The CD4/CD8 ratio never exceeded 0.71, whereas the lowest ratio in controls was 0.81: this difference was statistically significant (P=0.0009). The mean number of Langerhans cells was markedly reduced in the high-grade SILs in the HIV patients in comparison with controls (P=0.001). The number of CD4 cells and the CD4/CD8 ratio correlated with the peripheral CD4 count (P=0.001 and 0.02). Conclusions In our study a marked local impairment of cervical immunoreactivity was observed, which may play a major role in the progression of these lesions in HIV-infected women.


2010 ◽  
Vol 7 (1) ◽  
pp. 382-388
Author(s):  
Baghdad Science Journal

This study aimed to isolate and phenotype lymphocytes in untreated children patients with chronic allergic asthma. To reach such aim the study involved (25) patients from children (17 male and 9 female) whom their ages where between (3-10) years, in addition to (15) apparently healthy children (9 male and 6 female) in the same ages involved as control group. The data demonstrated that there was a significant increase in the mean percentages of T-lymphocytes (CD3+ cells) in the peripheral blood of patients (66.75±0.29)**, in comparison with control group (43.58±0.19), a significant increase in the mean percentages of T-helper lymphocytes (CD4+ cells) in the peripheral blood of patients (51.14±0.55), in comparison with control group (39.17±0.23) and the mean percentages of B-lymphocytes (CD20+ cells) was also increased significantly in the peripheral blood of patients (29.63±0.20) when it compared with the mean percentages of the same cells in control group (18.60±0.80). Besides a significant decrease in the mean percentages of T-suppressor lymphocytes (CD8+ cells) in the peripheral blood of patients (11.31±0.05), in comparison with control group (16.42±0.15). Finally the results of this study showed a significant increase in the mean percentages of the ratio of (CD4+ cells/CD8+ cells) in the peripheral blood of patients (55.34±0.41), in comparison with control group (31.25±0.09).


2021 ◽  
Vol 9 (B) ◽  
pp. 1621-1624
Author(s):  
Cahyono Hadi ◽  
Cipta Pramana

BACKGROUND: The 2019 coronavirus disease has been declared by WHO as a pandemic that has spread throughout the world since March 2020. AIM: This study was conducted to determine the profile of COVID-19 patients at Dr. Moewardi hospital Surakarta. METHODS: This study is a retrospective descriptive study, with the population and study samples taken from medical records of patients with a diagnosis of COVID-19 or SARS-CoV-2. RESULTS: male sex with a total of 42 patients (47.72%) and female sex 46 patients (52.57%). The highest age group was in the age group 40-59 years with 46 patients (52.27%), with the most comorbid history being cardiovascular disease 31 patients (35.22%). The mean cytokine analysis of 88 patients includes examination of IL-1 that is equal to 73.95 and TNF-α with a mean of 67.19. The mean shows an increase above the normal value. CONCLUSION: There is no difference between the sexes of men and women. The highest age range is in the 40-59-year age group. The most common comorbid history is cardiovascular disease. And the average patient showed increased levels of IL-1 and TNF-α.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 530-530 ◽  
Author(s):  
Ulf-Henrik Mellqvist ◽  
Jan Westin ◽  
Peter Gimsing ◽  
Oyvind Hjertner ◽  
Stig Lenhoff ◽  
...  

Abstract Abstract 530 An open, multi-center, randomized phase III trial performed by the Nordic Myeloma Study Group (NMSG) was designed to explore the effect of a 21-week consolidation period of single agent bortezomib, given during months 3-8 after ASCT. Primary end-point was event free survival and secondary end-points were response rate, toxicity, overall survival, quality of life and cost utility. Between November 2005 and April 2009 404 patients were included, 372 of whom were randomized. This report comprises preliminary data concerning feasibility, toxicity and response rate for the initial 299 randomized patients. Patients were randomized 3 months post ASCT to either no consolidation therapy (current standard in Scandinavia), or to a period of bortezomib consolidation. Initial treatment before ASCT was optional. Patients were stratified for single or double ASCT. Bortezomib was given in a dose of 1.3 mg/m2 twice weekly (days 1, 4, 8 and 11) in a 3 week schedule for the first 2 cycles. In the following four cycles, bortezomib was given once weekly (days 1, 8 and 15) in a 4 week schedule, in total 20 injections over 21 weeks. Before each dose of study drug, the patients were evaluated for possible toxicities. Baseline characteristics were well balanced between the 149 patients in the bortezomib group and the 150 in the control group. All analyses were performed on an intention to treat basis. The mean number of bortezomib injections was 15, median 19 of optimal 20. The mean total dose given was 82 %, median 90 %, of the planned dose. Thirty-one patients (21 %) had to reduce the dose to zero for one cycle or more, mainly due to neuropathy, 11 patients, or progression, 8 patients. Hematological toxicity according to CTC included neutropenia grade ≥ III in 33 patients (22 %), thrombocytopenia grade ≥ III in 14 patients (9 %). Neurological pain grade ≥ III was seen in 7 patients (5 %). Sensory neuropathy grade ' III was seen in 5 patients (3 %). A significant difference in improvement of response was noted between the two arms. At the time of randomization the proportion of CR/nCR was 23 % for patients in the bortezomib arm and 21 % in the control arm. However, when measured six months after randomization (9 months after ASCT), the proportion of CR/nCR was 54 % in the bortezomib group versus 35 % for the controls, p < 0.005. The proportion of patients improving their response from PR to CR/nCR was 20 % and 12 % for the bortezomib and control groups respectively, p = 0.06 NS. The proportion of patients who relapsed during the initial 6 month observation period did differ significantly, 1 % versus 6 %, p<0.05. Our results indicate that consolidation with bortezomib given as a single agent is feasible and does improve treatment response after ASCT. Disclosures: Mellqvist: Jansen-Cilag: Speakers Bureau; Celgene: Speakers Bureau; Johnson and Johnson: Research Funding. Off Label Use: Bortezomib. Consolidation therapy after high dose melphalan.. Westin:Celgene: Membership on an entity's Board of Directors or advisory committees. Gimsing:Jansen-Cilag: Membership on an entity's Board of Directors or advisory committees; GenMab: Membership on an entity's Board of Directors or advisory committees; Schering-Plough: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Laane:Schering-Plough: Membership on an entity's Board of Directors or advisory committees. Remes:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jansen-Cilag: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Waage:Jansen-Cilag: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genzyme: Membership on an entity's Board of Directors or advisory committees.


2002 ◽  
Vol 9 (2) ◽  
pp. 279-281 ◽  
Author(s):  
Abdulla Al Qouzi ◽  
Abdulla Al Salamah ◽  
Reem Al Rasheed ◽  
Abdulla Al Musalam ◽  
Khalid Al Khairy ◽  
...  

ABSTRACT Flow cytometry is an important tool for the diagnosis and follow-up of immunodeficiency patients, as well as for pateints with leukemia and lymphoma. Lymphocytes and their subsets show variations with race. The aim of this study was to establish reference ranges for lymphocytes and their subsets in an Saudi adult population by using flow cytometry. Blood samples obtained from 209 healthy Saudi men were used for this study. All blood donors were between 18 and 44 years old. Lymphocytes and their subsets were analyzed by flow cytometry, and the absolute and percentage values were calculated. We investigated the expression of T-cell markers (CD3, CD4, and CD8), B cells (CD19), and natural killer cells (CD16 and CD56). The absolute and percent values of each cell subset were compared with published data from different populations by using the Student t test. Reference ranges, each expressed as the mean ± the standard deviation, were as follows: leukocytes (6,335 ± 1759), total lymphocytes (2,224 ± 717), CD3 cells (1,618 ± 547), CD4 cells (869 ± 310), CD8 cells (615 ± 278), CD19 cells (230 ± 130), and CD3-CD16+/CD56+ cells (262 ± 178). The CD4/CD8 ratio was 1.6 ± 0.7. Our results for B cells, CD4 cells, and CD8 cells and for the CD4/CD8 ratio fell in between the reported results for Ethiopian and Dutch subjects. Our results were also different from previously reported findings in an Saudi adult population that showed no increase in CD8 T cells. We thus establish here the reference ranges for lymphocytes and their subsets in a large cohort of Saudi men. The CD8 cell count was not abnormally high, as previously reported, and fell in between previous results obtained for African and European populations.


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