Prognostic Impact of Bone Marrow Fibrosis and Effects of Tyrosine Kinase Inhibitors on Bone Marrow Fibrosis in Chronic Myeloid Leukemia.

BACKGROUND: Myelofibrosis is reported in around 40% of newly diagnosed chronic myeloid leukemia (CML) patients and have an important role in the pathobiology and prognosis of CML. This retrospective study aimed to evaluate the effects of bone marrow (BM) fibrosis on disease prognosis and the effects of specific tyrosine-kinase inhibitors (TKIs) on BM fibrosis in CML patients. METHODS: The study included 96 patients (>18 years) diagnosed with chronic phase (CP) CML. The clinical and demographic information were collected from the medical files. Post-treatment BM aspirate and core biopsy samples were analyzed for the presence of fibrosis and dysplasia. RESULTS: The mean age of the study patients was 52.69 years; 47.9% of the patients were female. At the onset, 53 (63.1%) patients had BM fibrosis. The difference in the overall survival of the patients with respect to BM fibrosis grades was significant (p = .001). Within the BM fibrosis grade groups, there were significant differences between grade 0 vs. grade 2, grade 0 vs. grade 3, and grade 1 vs. grade 3 (p = .005, p = .002, and p = .003 respectively) There was no significant association between the presence of BM fibrosis at the onset and not responding to first-line therapy (p = .724). Moreover, no significant association was found between the presence of BM fibrosis at the onset and molecular (p = .623) or cytogenetic response (p = .535) to first-line therapy. Additionally, the association between the type of second-line and third-line therapy and molecular response (p = .773 and p = .424, respectively) or cytogenetic response (p = .298 and p = .641) was not significant. CONCLUSION: Although BM fibrosis seems to be a crucial complication of CML with a poor prognosis, it can be reversed via TKI treatment which may result in improved survival. It might be considered to check the BM for this complication on a regular basis during therapies to test its prognostic influence in CML patients in prospective controlled trials. Further studies focused on this issue are required to utilize BM fibrosis as a candidate prognostic factor.

Comparison of maintenance regimens in Acute Promyelocytic Leukemia patients.

Maintenance therapy in APL is still a standard especially in high-risk patients treated with chemotherapy+ATRA combination whereas the role of the maintenance therapy in low-risk patients is controversial. This study aims to compare the efficacy and toxicity of ATRA monotherapy and ATRA+MTX+ 6-MP combination as the maintenance treatment for 2 years in APL patients who achieved molecular complete response after induction and consolidation with ATRA+chemotherapy. A total of 71 patients from 4 different centers were included in this study. After a median follow-up of 54 months (5-180 months), the 5-year RFS was 89 % in the ATRA monotherapy arm, the 5-year RFS was 78.5 % in the combined treatment arm (p = 0.643, HR:1.3, 95 % CI: 0.35-5.3). Hematological toxicity in all grades and Grade III/IV hematological toxicity was observed significantly more in the combined treatment arm than in the ATRA monotherapy arm (All grades: 76.9 % vs 18.9 %, p < 0.001; Grade III/IV: 20.5 % vs. 3.1 %, p = 0.035). Hepatotoxicity at all levels was significantly higher in the combined treatment arm than in the ATRA monotherapy arm (61.5 % vs 25 %, p = 0.002). Our study concluded that two years of ATRA monotherapy and combined maintenance therapy, both of which were found to be similar in terms of disease control and long term survival, ATRA Monotherapy could be a safer maintenance treatment option since both hematological and non-hematological toxicities were observed less often in the ATRA monotherapy arm.

A novel differential diagnosis algorithm for chronic lymphocytic leukemia using immunophenotyping with flow cytometry.

INTRODUCTION: The availability of a clinical decision algorithm for diagnosis of chronic lymphocytic leukemia (CLL) may greatly contribute to the diagnosis of CLL, particularly in cases with ambiguous immunophenotypes. Herein we propose a novel differential diagnosis algorithm for the CLL diagnosis using immunophenotyping with flow cytometry. METHODS: The hierarchical logistic regression model (Backward LR) was used to build a predictive algorithm for the diagnosis of CLL, differentiated from other lymphoproliferative disorders (LPDs). RESULTS: A total of 302 patients, of whom 220 (72.8%) had CLL and 82 (27.2%), B-cell lymphoproliferative disorders other than CLL, were included in the study. The Backward LR model comprised the variables CD5, CD43, CD81, ROR1, CD23, CD79b, FMC7, sIg and CD200 in the model development process. The weak expression of CD81 and increased intensity of expression in markers CD5, CD23 and CD200 increased the probability of CLL diagnosis, (p < 0.05). The odd ratio for CD5, C23, CD200 and CD81 was 1.088 (1.050 - 1.126), 1.044 (1.012 - 1.077), 1.039 (1.007 - 1.072) and 0.946 (0.921 - 0.970) [95% C.I.], respectively. Our model provided a novel diagnostic algorithm with 95.27% of sensitivity and 91.46% of specificity. The model prediction for 97.3% (214) of 220 patients diagnosed with CLL, was CLL and for 91.5% (75) of 82 patients diagnosed with an LPD other than CLL, was others. The cases were correctly classified as CLL and others with a 95.7% correctness rate. CONCLUSIONS: Our model highlighting 4 markers (CD81, CD5, CD23 and CD200) provided high sensitivity and specificity in the CLL diagnosis and in distinguishing of CLL among other LPDs.

A novel differential diagnosis algorithm for chronic lymphocytic leukemia using immunophenotyping with flow cytometry

Abstract Introduction The availability of a clinical decision algorithm for diagnosis of chronic lymphocytic leukemia (CLL) may greatly contribute to the diagnosis of CLL, particularly in cases with ambiguous immunophenotypes. Herein we propose a novel differential diagnosis algorithm for the CLL diagnosis using immunophenotyping with flow cytometry. Methods The hierarchical logistic regression model (Backward LR) was used to build a predictive algorithm for the diagnosis of CLL, differentiated from other lymphoproliferative disorders (LPDs). Results A total of 302 patients, of whom 220 (72.8%) had CLL and 82 (27.2%), B-cell lymphoproliferative disorders other than CLL, were included in the study. The Backward LR model comprised the variables CD5, CD43, CD81, ROR1, CD23, CD79b, FMC7, sIg and CD200 in the model development process. The weak expression of CD81 and increased intensity of expression in markers CD5, CD23 and CD200 increased the probability of CLL diagnosis, (p < 0.05). The odd ratio for CD5, C23, CD200 and CD81 was 1.088 (1.050 - 1.126), 1.044 (1.012 - 1.077), 1.039 (1.007 - 1.072) and 0.946 (0.921 - 0.970) [95% C.I.], respectively. Our model provided a novel diagnostic algorithm with 95.27% of sensitivity and 91.46% of specificity. The model prediction for 97.3% (214) of 220 patients diagnosed with CLL, was CLL and for 91.5% (75) of 82 patients diagnosed with an LPD other than CLL, was others. The cases were correctly classified as CLL and others with a 95.7% correctness rate. Conclusions Our model highlighting 4 markers (CD81, CD5, CD23 and CD200) provided high sensitivity and specificity in the CLL diagnosis and in distinguishing of CLL among other LPDs.

Turkey real-life data: demographic features, treatment results and effects of comorbidities in chronic myeloid leukemia.

Aim: This study aimed to identify patient characteristics, treatment patterns and outcomes and to evaluate the effects of presence of comorbidities at diagnosis in chronic phase (CP)-chronic myeloid leukemia (CML) patients in Turkey. Materials & methods: Hospital records between 2005 and 2018 were retrospectively reviewed. Results: Of 861 CP-CML patients included, 31% had at least one comorbidity at diagnosis. Sex, cardiovascular disease status at diagnosis and molecular (at least major) and cytogenetic (partial and complete) responses were the independent predictors of survival. Conclusion: The response rates of CP-CML patients to the tyrosine kinase inhibitors were satisfactory. In addition to tolerability and side effect profiles of drugs, comorbidity status of patients should also be considered in treatment choice in CML patients.

This study aimed to identify patient characteristics, treatment patterns and outcomes and to evaluate the effects of presence of comorbidities at diagnosis in chronic phase (CP)-chronic myeloid leukemia (CML) patients in Turkey. Hospital records of patients between 2005 and 2018 were retrospectively reviewed. Of the included 861 CP-CML patients, 31% had at least one comorbidity at diagnosis. The survival of the patients was affected by sex, cardiovascular disease status at diagnosis, and molecular (at least major) and cytogenetic (partial and complete) responses. The response rates of CP-CML patients to the tyrosine kinase inhibitors were satisfactory. In addition to tolerability and side effect profiles of drugs, comorbidity status of patients should also be considered in treatment choice in CML patients.

Predictive Factors for Molecular Response in Chronic Myeloid Leukemia: Reduction Ratio and Halving Time of BCR::ABL1 IS Transcript Levels

Objective: Achieving an early molecular response (EMR) is crucial for improving the prognosis of patients with chronic myeloid leukemia (CML). The halving time (HT) and reduction ratio (RR) of BCR::ABL1 transcript levels have recently emerged as additional prognostic indexes besides the BCR::ABL1 International Scale (IS). We aimed to investigate the prognostic role of BCR::ABL1 transcript levels, HT, and RR on molecular response kinetics at 3 months in patients with newly diagnosed chronic-phase (CP)-CML. Materials and Methods: Forty patients with CP-CML who received first-line imatinib treatment were included in this study. BCR::ABL1 transcript levels and molecular responses at baseline and at 3, 6, 12, and 24 months of treatment were evaluated retrospectively. Major molecular response (MMR) at 12 months and event-free survival (EFS) were determined as primary endpoints and the effects of treatment kinetics on these parameters were examined. Results: Of the 40 patients, BCR::ABL1 IS was ≤10% at 3 months in 72.5%, representing EMR. The rate of event occurrence was 45.5% in patients with BCR::ABL1 IS of >10%, whereas it was 6.9% in those with BCR::ABL1 IS of ≤10% (p=0.004). MMR was detected in 62.1% of the patients with EMR and in 9.1% of those without EMR (p=0.003). The cut-off value for achieving MMR was 24 days for HT and 0.04 for RR. Deep molecular response (DMR) at 24 months was associated with HT of ≤24 days and RR of ≤0.04. EFS was found to be significantly better in the group with BCR::ABL1 IS of ≤10% and HT of ≤24 days (p=0.001) and in the group with BCR::ABL1 IS of ≤10% and RR of ≤0.04 (p=0.007) compared to others. Conclusion: Our findings revealed that MMR could be predicted via EMR as well as by HT and RR. Additionally, HT of ≤24 days and RR of ≤0.04 were more important than BCR::ABL1 IS of ≤10% in achieving DMR at 24 months, and the combination of BCR::ABL1 IS of ≤10% with both HT of ≤24 days and RR of ≤0.04 has the best predictive value for EFS.

The evaluation of patients with essential thrombocythemia in terms of risk of thrombosis.

OBJECTIVE: The aim of this study was to compare the incidence of factors associated with an increased risk of thrombosis in patients with essential thrombocythemia. METHODS: A total of 200 patients followed-up in our unit with a diagnosis of essential thrombocythemia in 13 years were analyzed retrospectively. RESULTS: Of the study participants, 60.5% were females and 39.5% were males, with an overall mean (±SD) age of 54.93 (±14.21) years. In 119 patients, Janus Kinase 2 was positive with 56.3% of cases. When two patient categories were defined as those with or without history of thrombosis, no significant differences were found in terms of Janus Kinase 2 positivity, mean age, as well as white blood cells and platelet counts (p>0.05). Also, no significant differences in thrombotic event incidence were found between patient categories defined on the basis of cut-off values for white blood cells (cut-off values of 15×103/mm3 and 8.7×103/mm3) and platelets (cut-off values of 1500×103/mm3) (p>0.05). CONCLUSION: Although our results are generally in line with the published data, some divergence from previous results has been observed with respect to risk factors for thrombotic events. Absence of a correlation between leukocytosis and thrombosis may be related with the significant decline in white blood cells after treatment. Also, a significant reduction in platelet counts occurring in association with treatment is linked with a lowered incidence of thrombosis. Janus Kinase 2-positive patients had a similar thrombosis frequency with that reported in the literature.

Conditioning Regimens for Relapsed/Refractory Lymphoma Patients Undergoing Autologous Stem Cell Transplantation: BEAM Versus High Dose ICE.

There are different drug combinations and conditioning regimens in lymphoma transplants. However, no randomized data is available to demonstrate the superiority of any regimen and the optimal choice is unknown. In this analysis, we compared the efficacy, toxicity and the survival outcomes of the BEAM and the high dose ICE (hdICE) conditioning regimens in relapsed NHL and relapsed/refractory Hodgkin Lymphoma patients undergoing auto-SCT. 83 patients with relapsed/refractory HL or relapsed NHL who were treated with Auto-SCT between 2006 and 2016, were analyzed retrospectively. 52 patients (62.7%) received BEAM, while 31 patients (37.3%) received hdICE. Between two groups there is no significant difference in age, gender, diagnosis, disease stage, chemosensitivity, ECOG performance status, time from diagnosis to transplant, salvage regimens and previous lines of chemotherapy. After a median of 59-month follow-up, PFS and OS rates of both groups were similar (5-year PFS was 51.6% in BEAM group, 48.8% in hdICE group, p = 0.71; 5-year OS was 58% in BEAM group, 54.8% in hdICE group, p = 0.93). The median neutrophil (11 vs. 10 days, p = 0.06) and platelet engraftment (13 vs. 11 days, p = 0.01) was faster and demand of transfusions were lesser in hdICE group (p = 0.03). However, severe renal toxicity was significantly higher in hdICE group in our study (p = 0.01). hdICE conditioning regimen may be used as an alternative to BEAM, with similar survival outcomes and toxicity profile, especially transplant centers that experience some difficulties in the availability of the carmustine.

Efficacy and safety of ruxolitinib in patients with myelofibrosis: a retrospective and multicenter experience in Turkey

Background/aim: The aim of this study is to assess the efficacy and safety of ruxolitinib in patients with myelofibrosis. Materials and methods: From 15 centers, 176 patients (53.4% male, 46.6% female) were retrospectively evaluated. Results: The median age at ruxolitinib initiation was 62 (28­87) and 100 (56.8%) of all were diagnosed as PMF. Constitutional symptoms were observed in 84.7%. The median initiation dose of ruxolitinib was 30 mg (10­40). Dose change was made in 69 (39.2%) patients. Forty seven (35.6%) and 20 (15.2%) of 132 patients had hematological and nonhematological adverse events, respectively. The mean spleen sizes before and after ruxolitinib treatment were 219.67 ± 46.79 mm versus 199.49 ± 40.95 mm, respectively (p < 0.001). There was no correlation between baseline features and subsequent spleen response. Overall survival at 1-year was 89.5% and the median follow up was 10 (1­55) months. We could not show any relationship between survival and reduction in spleen size (p = 0.73). Conclusion: We found ruxolitinib to be safe, well tolerated, and effective in real-life clinical practice in Turkey. Ruxolitinib dose titration can provide better responses in terms of not only clinical benefit but also for long term of ruxolitinib treatment.

Is dynamic thiol/disulfide homeostasis associated with the prognosis of myelodysplastic syndrome?

BACKGROUND: This study planned to investigate the relationship of dynamic thiol/disulfide homeostasis with the prognosis of myelodysplastic syndrome (MDS). METHODS: 80 patients who had been diagnosed with MDS between 2012 and 2017 and who were older than 18 were included in the study together with 80 healthy control subjects. The MDS diagnosis was confirmed using bone marrow aspiration-biopsy immunostaining. Dynamic thiol/disulfide homeostasis and ischemia-modified albumin (IMA) levels were examined. RESULTS: The average IMA (0.71±0.08 vs. 0.67±0.09; p=0.002), median disulfide (18.0 vs. 11.6; p<0.001), median disulfide/native thiol (6 vs. 3; p<0.001), and median disulfide/total thiol (5.4 vs. 2.9; p<0.001) were found higher in the MDS patients compared to control group, and the median hemoglobin, median white blood cell count, median neutrophil count, median lymphocyte count, average native thiol (290.7±48.5 vs. 371.5±103.8; p<0.001), average total thiol (328.2±48.9 vs. 393±105.5; p<0.001), and average native thiol/total thiol (%) (88.3±4.3 vs. 94.2±2.1; p<0.001) were found to below. Risk factors such as collagen tissue disease (HR:9.17; p=0.005), MDS-EB-1 (HR:10.14; p=0.032), MDS-EB-2 (HR:18.2; p=0.043), and disulfide/native thiol (HR:1.17; p=0.023) were found as the independent predictors anticipating progression to acute myeloid leukemia. In the Cox regression model, risk factors such as age (HR:1.05; p=0.002), MDS-EB-1 (HR:12.58; p<0.001), MDS-EB-2 (HR:5.75; p=0.033), disulfide/native thiol (HR:1.14; p=0.040), and hemoglobin (HR:0.64; p=0.007) were found as predictors anticipating for mortality. CONCLUSIONS: We can argue that dynamic thiol/disulfide homeostasis could have significant effects on both the etiopathogenesis and the survival of patients with MDS, and it could be included in new prognostic scoring systems.

Comparison of allogenic stem cell transplantations performed with frozen or fresh stem cell products with regard to GVHD and mortality.

PURPOSE: Stem cells are collected from donors and infused to the recipient in allogenic peripheral stem cell transplantations. The use of frozen stem cells can promote donor compatibility, and overcoming possible problems due to insufficient stem cell mobilization will also be easier. Nevertheless, studies about the use of frozen peripheral stem cells in allogenic transplantation are extremely rare. In this study, we aimed to compare the clinical outcomes of allogenic stem cell transplants from frozen or fresh stem cell products. MATERIALS AND METHODS: This retrospective analysis was conducted between April 2004 and September 2018 in the bone marrow transplantation unit of Ankara Numune Training and Research Hospital. Clinical data of patients who received allogenic peripheral stem cell transplantations from fully matched sibling donors were compared for 42 fresh and 30 frozen stem cell transplants. RESULTS: While the platelet engraftment period, febrile neutropenia period, hospitalization period, and 100-day mortality rates did not show any differences, the neutrophil engraftment period was longer in the frozen group (mean: 14 days vs. 16 days, p = 0.006). Acute and chronic graftversus-host disease (GVHD) rates were similar in both groups; however, the rate of grade 3 or4 chronic liver GVHD was slightly higher in transplants performed with fresh stem cells compared to the frozen group (p = 0.046). Overall survival was similar between the groups (p = 0.700). CONCLUSION: The use of frozen peripheral stem cells in allogenic stem cell transplantation may be a reasonable option that can be applied without causing a significant change in clinical results.

The Importance of RET-He in the Diagnosis of Iron Deficiency and Iron Deficiency Anemia and the Evaluation of Response to Oral Iron Therapy.

BACKGROUND: The purpose of this study is to investigate whether or not reticulocyte hemoglobin equivalent (RET-He) is a superior indicator of blood count and other iron parameters in terms of diagnosing iron deficiency (ID) and iron deficiency anemia (IDA), and thus evaluating a patient's response to oral iron treatment. METHODS: The research population consisted of 217 participants in total: 54 control, 53 ID, 58 non-ID anemia, and 52 IDA patients. A hemoglobin (Hb) value of < 130.0 g/L was defined as indicating anemia for men, while an Hb value of < 120.0 g/L was defined as indicating anemia for women. All patients were administered 270 mg oral elemental iron sulphate daily. RESULTS: The RET-He was significantly lower in the IDA group, compared to other groups (IDA: 21.0 ± 4.1, ID: 26.0 ± 4.9, non-ID anemia: 32.1 ± 6.8, control: 36.6 ± 7.0; < 0.001). The ID group had a lower RET-He compared to the non-ID anemia group and the control group. On the 5th day of treatment, the ID and IDA group showed no significant differences in terms of Hb while the RET-He level demonstrated a significant increase. The increase in the RET-He level observed in the IDA group on the 5th day was significantly higher compared to the increase observed in the ID group. A RET-He value of 25.4 pg and below predicted ID diagnosis with 90.4% sensitivity and 49.1% specificity in IDA patients, compared to the ID group. CONCLUSIONS: The results of our study, therefore, suggest that RET-He may be a clinically useful marker in the diagnosis of ID and IDA.

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective: The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods: A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm3). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed. Results: The median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6%), weakness (13.7%), hepatotoxicity (11.8%), and thrombosis (5.9%). Conclusion: Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.

The Role of CD200 and CD43 Expression in Differential Diagnosis between Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma.

OBJECTIVE: Atypical chronic lymphocytic leukemia (CLL) is most frequently confused with mantle cell lymphoma (MCL). Several markers may contribute to the diagnosis of CLL. However, there is no consensus on which markers are needed to be used in flow cytometry for the diagnosis of CLL. The aim of the present study was to investigate the role of CD43 and CD200 markers in the differential diagnosis between CLL and MCL. MATERIALS AND METHODS: To address this issue, 339 consecutive patients with CLL and MCL were included in the flow cytometry lymphoproliferative disease panel for evaluation of CD43 and CD200 expressions, but not in the Matutes scoring system. RESULTS: CD200 was expressed in 97.3% of atypical CLL cases, whereas it was dimly expressed in only 6.1% of MCL cases. CD43 expression was 95.7% in atypical CLL cases. In the MCL cases, its expression rate was 39.4%. CONCLUSION: CD43 and CD200 were found to be more valuable markers than CD22, CD79b, and FMC7. CD43 and CD200 could also be considered as definitive markers in atypical CLL patients, for whom the Matutes scoring system remains ineffective.

The Assessment of CD56 and CD117 Expressions at the Time of the Diagnosis in Multiple Myeloma Patients.

OBJECTIVE: The purpose of this study is to investigate the relationship between the CD56 and CD117 expressions and the clinical and laboratory findings in multiple myeloma (MM) patients. MATERIALS AND METHODS: Analyses of multiparametric flow cytometry data obtained from the diagnostic bone marrow aspirations of a total of 34 newly diagnosed MM patients were assessed retrospectively. CD56 and CD117 expressions of the patients were compared with their stages and clinical parameters. The staging was performed according to the International Staging System (ISS). RESULTS: Of the patients, 58.8% had ISS stage 1-2 MM while 41.2% had stage 3 MM. The number of CD56-positive patients was 29, whereas the number of CD117-positive patients was 13. There was no statistical difference between the CD56 and CD117 expressions and extramedullary involvement and lytic bone lesions. The median beta-2 microglobulin level was higher in the CD117-negative group (p=0.047). CD56 and CD117 expression levels were found to be lower in advanced-stage patients than in early-stage ones (p=0.026 and p=0.017). The lactate dehydrogenase (LDH) levels were high in advanced-stage patients, and an inverse relationship was found between LDH level and CD117 expression. CONCLUSION: Our findings that the CD56 and CD117 expression levels are lower in advanced stages than earlier stages and that LDH level and CD117 expression have an inverse relationship in patients with newly diagnosed MM suggest that CD56 and CD117 expressions may be prognostic markers for MM.

CD38 Expression and Variation as a Prognostic Factor Chronic Lymphocytic Leukemia.

BACKGROUND: In this study, we aimed to determine a cutoff level for CD38 that would aid us in identifying chronic lymphocytic leukemia patients in need of early therapy and predicting patients at sufficiently low risk who would likely exhibit a rapid improvement; we also aimed to find out if CD38 expression would show variability during disease course and determine the extent of CD38 expression. METHODS: 124 patients were diagnosed with CLL. CD38 and ZAP-70 expression levels were measured with four color flowcytometry. Time from diagnosis to initial therapy was calculated for all patients. CD38 expression was studied for a second time during follow-up in 50 patients. RESULTS: For cutoff levels of 7%, 20%, and 30%, CD38 expressions were 61.3%, 25%, and 24.2%, respectively. At all three cutoff levels there were significant correlations with all parameters except age between CD38+ vs. CD38- groups (p < 0.001). The comparative rates of starting therapy for cutoff levels of 7%, 20%, and 30% in CD38+ and CD38- groups were 77.5% vs. 6.25%; 100% vs. 30.7%, and 100% vs. 31.5%, respectively (p < 0.001). Multiple Cox Proportional Hazards Regression analysis: for a cutoff level of 7%, survival was affected by STAGE, ZAP70, and CD38. CONCLUSIONS: A CD38 cutoff level of 7% determined by standardized laboratory techniques is an important prognostic marker. However, the number and frequency of repeat measurements of CD38 expression, and cutoff level of CD38 expression that significantly predict disease prognosis should be further determined by future cohort studies.

Determination of HLA-G Expression and Evaluation of Its Role as a Prognostic Factor in Chronic Lymphocytic Leukemia.

BACKGROUND: In recent years, the clinical and biological features governing the clinical course of chronic lymphocytic leukemia (CLL) have been most extensively studied. Human leukocyte antigen-G (HLA-G) allows tumor cells to escape from the antitumor effect of the immune system. Recent studies have shown that various tumor cells show an increased HLA-G expression. Data regarding HLA-G expression in CLL are limited and controversial. The aim of this work is to evaluate flow cytometry study of HLA-G expression on cell surface and assess its relationship with other prognostic factors (CD38, ZAP70, beta 2 microglobulin [ß2MG]) in patients with CLL. DESIGN AND METHODS: Forty-five newly diagnosed CLL cases. White blood cell count, lymphocyte absolute count, hemoglobin level, platelet count, serum lactate dehydrogenase activity, and serum ß2MG level were studied at admission. In each patient, morphologic diagnosis of B-CLL was confirmed by flow cytometry HLA-G, CD38 and ZAP70 expression levels were measured with four-color flow cytometry. RESULTS: HLA-G positivity ranged between 1% and 12% in CLL patients. A significant correlation was found with CD38, ZAP70, disease stage, and ß2MG (P < 0.001). The off-treatment follow-up period was longer in the HLA-G negative group (P < 0.022). CONCLUSIONS: In conclusion, we suggest that, in addition to other prognostic factors, surface HLA-G expression can be considered as an independent prognostic factor. However, our work should be confirmed by further prospective studies, a longer off-treatment follow-up period, and a standardized method.

Serum thrombin activatable fibrinolysis inhibitor levels in patients with newly diagnosed multiple myeloma.

Multiple myeloma has been associated with the development of thromboembolic events. Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme, which potently inhibits fibrinolysis. The purpose of the present study was to assess the TAFI levels in patients with newly diagnosed multiple myeloma. Twenty-seven newly diagnosed multiple myeloma patients (16 women and 11 men) and 27 age-matched healthy individuals (14 women and 13 men) were included in the study. Serum TAFI levels were significantly increased in patients with multiple myeloma (46 ± 13. 3 vs. 36. 6 ± 9.7 µg/ml) compared with healthy individuals. Serum TAFI levels were negatively correlated with serum albumin (CC: -0.453, P < 0.05) and hemoglobin levels (CC: -0.392, P < 0.05) and positively correlated with the ß-2 microglobulin levels (CC: 0.524, P < 0.05). In this study, we observed significantly elevated TAFI levels in patients with multiple myeloma and higher serum TAFI levels were suggested to be associated with higher disease stage. With these results, a possible role of elevated TAFI levels in thromboembolic manifestations in the course of multiple myeloma can be suggested.

A rare extramedullary involvement in myeloma: lung parenchyma and association with unfavorable chromosomal abnormalities.

Although pulmonary complications developing secondary to lung infections and involvement in ribs occur frequently in multiple myeloma (MM), involvement of the lung parenchyma is quite rare. In clinical studies, the involvement of lung parenchyma has been found to be associated with unfavorable prognosis. Here, a MM case in whom involvement of lung parenchyma was accompanied by unfavorable prognostic cytogenetic markers is presented. A 62-year-old male presented with complaint of cough, and heterogeneous hypodense mass was detected in thorax computerized tomography. The patient underwent bronchoscopic biopsy. Pathological examination revealed diffuse plasma cell infiltration staining with kappa immunohistochemically. In bone marrow biopsy, plasma cell infiltration was observed. In conventional cytogenetic examination, hypodiploidy was established. In cytogenetic examination carried out with fluorescence in situ hybridization, deletion (13q) was determined. In conclusion, in patients diagnosed with MM and presenting with pulmonary mass lesion, lung involvement associated with plasma cell infiltration should also be considered in the differential diagnosis. As overall survival is low in these cases, more aggressive treatment approaches such as high-dose treatment should be immediately considered.