Although dose-intensive strategies or high-dose therapy induction followed by autologous stem-cell transplantation have improved the outcome for patients with mantle-cell lymphoma (MCL), most ...eventually relapse and subsequently respond poorly to additional therapy. Bortezomib (in the United States) and temsirolimus (in Europe) are currently the only two treatments approved for relapsed disease. Lenalidomide is an immunomodulatory agent with proven tumoricidal and antiproliferative activity in MCL. The MCL-001 (EMERGE) trial is a global, multicenter phase II study examining the safety and efficacy of lenalidomide in patients who had relapsed or were refractory to bortezomib.
Lenalidomide 25 mg orally was administered on days 1 through 21 every 28 days until disease progression or intolerance. Primary end points were overall response rate (ORR) and duration of response (DOR); secondary end points included complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and safety.
In all, 134 patients were enrolled with a median age of 67 years and a median of four prior therapies (range, two to 10 prior therapies). The ORR was 28% (7.5% CR/CR unconfirmed) with rapid time to response (median, 2.2 months) and a median DOR of 16.6 months (95% CI, 7.7 to 26.7 months). Median PFS was 4.0 months (95% CI, 3.6 to 5.6 months), and median OS was 19.0 months (95% CI, 12.5 to 23.9 months). The most common grade 3 to 4 adverse events were neutropenia (43%), thrombocytopenia (28%), anemia (11%), pneumonia (8%), and fatigue (7%).
The MCL-001 study demonstrated durable efficacy of lenalidomide with a predictable safety profile in heavily pretreated patients with MCL who had all relapsed or progressed after or were refractory to bortezomib.
Multiple myeloma (MM) is a haematological malignancy primarily affecting the elderly, with a striking male predilection and ethnic disparities in incidence. Familial predisposition to MM has long ...been recognized, but the genetic underpinnings remain elusive. This study aimed to investigate germline variants in Turkish families with recurrent MM cases. A total of 37 MM-affected families, comprising 77 individuals, were included. Targeted next-generation sequencing analysis yielded no previously reported rare variants. Whole exome sequencing analysis in 11 families identified rare disease-causing variants in various genes, some previously linked to familial MM and others not previously associated. Notably, genes involved in ubiquitination, V(D)J recombination and the PI3K/AKT/mTOR pathway were among those identified. Furthermore, a specific variant in BNIP1 (rs28199) was found in 13 patients across nine families, indicating its potential significance in MM pathogenesis. While this study sheds light on genetic variations in familial MM in Turkey, its limitations include sample size and the absence of in vivo investigations. In conclusion, familial MM likely involves a polygenic inheritance pattern with rare, disease-causing variants in various genes, emphasizing the need for international collaborative efforts to unravel the intricate genetic basis of MM and develop targeted therapies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective
Hyperinflammation (HI) that develops in week 2 of COVID‐19 contributes to a worse outcome. Because week 2 laboratory findings can be relatively mild, the available criteria for ...classification of hemophagocytic lymphohistiocytosis or macrophage activation syndrome are not helpful.
Methods
Our study included a discovery cohort of patients from Turkey with symptomatic COVID‐19 who were followed up while hospitalized during the initial wave and a replication cohort of hospitalized patients from a later period, all of whom required oxygen support and received glucocorticoids. Diagnosis of HI was made by an expert panel; most patients with COVID‐19–associated HI (HIC) received tocilizumab or anakinra. Clinical and laboratory data from start day of treatment with tocilizumab or anakinra in HIC patients were compared with the data from day 5–6 in patients without HIC. Values maximizing the sensitivity and specificity of each parameter were calculated to determine criteria items.
Results
The discovery cohort included 685 patients, and the replication cohort included 156 patients, with 150 and 61 patients receiving treatment for HI, respectively. Mortality rate in HI patients in the discovery cohort (23.3%) was higher than the rate in patients without HI (3.7%) and the rate in patients in the overall replication cohort (10.3%). The 12‐item criteria that we developed for HIC showed that a score of 35 provided 85.3% sensitivity and 81.7% specificity for identification of HIC. In the replication cohort, the same criteria resulted in 90.0% sensitivity for HIC; however, lower specificity values were observed because of the inclusion of milder cases of HIC responding only to glucocorticoids.
Conclusion
The use of the 12‐item criteria for HIC can better define patients with HIC with reasonable sensitivity and specificity and enables an earlier treatment start.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Primary focal segmental glomerulosclerosis (FSGS) treatment is based on immunosuppressive therapies. Since refractory disease is common, alternative methods are emerging. One of these ...methods is plasmapheresis with intravenous cyclosporine and corticosteroids, and it could be an option in post‐transplant recurrent FSGS. We retrospectively investigated the efficacy of this combined treatment in adult patients with refractory primary FSGS.
Methods
Seven refractory primary FSGS patients were included. Demographics, estimated glomerular filtration rates, serum albumin levels, urine protein/creatinine ratios, and previous treatments were evaluated. Also, complications and remission rates were assessed.
Results
Median patient age was 23 years. Median duration of diagnosis was 2 years. Median number of plasmapheresis sessions was 14. Five of seven patients (71.4%, one complete, four partial remissions) were responders after the protocol. Changes in serum albumin levels and proteinuria after protocol were statistically significant (P = 0.018 and P = 0.018, respectively). eGFR levels did not change statistically (P = 0.753). Median follow‐up duration after the treatment was 17 months. However, two patients experienced disease relapse (28.5%). End‐stage kidney disease was developed in two patients. Sustained remission rate was 42.8% during follow‐up (One complete and two partial remissions). Also, 42.8% of patients experienced catheter infections. Catheter‐associated thrombosis that required surgery was observed in a patient.
Conclusions
Plasmapheresis combined with intravenous cyclosporine and corticosteroids could be an option in refractory primary FSGS. High response rates after this protocol were encouraging. However, the relapsing disease was observed after the cessation of apheresis. Also, complications of the protocol could limit the applicability.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose
This study investigates the prognostic value of
68
Ga-Pentixafor PET/CT using PET-derived quantitative in multiple myeloma (MM) patients with suspected recurrence in comparison to
18
F-FDG ...PET/CT and clinical data.
Methods
Twenty-four MM patients with suspicion for relapse who underwent
68
Ga-Pentixafor and
18
F-FDG PET/CT were retrospectively evaluated. Total bone marrow glycolysis for
18
F-FDG (TBM
FDG
) and total bone marrow uptake for
68
Ga-Pentixafor PET/CT (TBM
CXCR4
) were calculated using whole-body metabolic tumor burden obtained by dedicated software (MIM 7.0.6). The patients were followed for 19–24 months, and the association of PET-derived quantitative data with overall survival (OS) was analyzed.
Results
68
Ga-Pentixafor PET/CT was positive in 17 patients, of which 13 were also positive on
18
F-FDG PET/CT, whereas 7 patients were negative on both scans. The positive rate of
68
Ga-Pentixafor and
18
F-FDG PET/CT on a patient-based approach was 70.8% and 54.1%, respectively.
68
Ga-Pentixafor positivity was significantly associated with OS (
p
= 0.009), and
18
F-FDG positivity was at the margin of statistical significance (
p
= 0.056). TBM
CXCR4
and TBM
FDG
were negatively correlated with OS (
r
= −0.457,
p
= 0.025 and
r
= −0.617,
p
= 0.001, respectively). The OS was negatively correlated with beta-2-microglobulin levels (
r
= −0.511,
p
= 0.01) and CRAB score (
r
= −0.592,
p
= 0.002) as an indicator of the end-organ disease, which confirmed these results. Serum beta-2-microglobulin levels and CRAB score were also correlated with TBM
CXCR4
(
r
= 0.442,
p
= 0.039 and
r
= 0.573,
p
= 0.003, respectively) and TBM
FDG
(
r
= 0.543,
p
= 0.009 and
r
= -0.424,
p
= 0.003, respectively).
Conclusion
68
Ga-Pentixafor PET/CT positivity is a negative prognostic factor in the survival outcome of MM patients. Complementary
68
Ga-Pentixafor PET/CT has the potential to overcome
18
F-FDG PET/CT limitations and helps a more precise risk stratification.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Redditux
(RED), as a biosimilar rituximab, was approved in Turkey for all indications of the original Mabthera
(MAB) in March 2018. The aim of our study was to evaluate the efficacy and safety of RED ...in de novo diffuse large B-cell lymphoma.
Fifty-one patients received RED combined with the CHOP regimen. The median follow-up was 31 months. The historical control group included 219 patients treated with the MAB-CHOP regimen and the median follow-up time was 38 months. We compared the response rates and survival outcomes of these RED-CHOP and MAB-CHOP cohorts.
In the RED cohort, the overall response rate (ORR) at the end of the treatment protocol was 86%, with 37 (72.5%) cases of complete response (CR) and 7 (13.5%) cases of partial response (PR). In the historical MAB cohort, the ORR was 84%, with CR and PR rates of 82% and 2%, respectively. The 24-month progression-free survival (PFS) rates were 73.76% (95% confidence interval CI: 0.59-0.84) and 85.2% (95% CI: 0.79-0.90) for the RED and MAB cohorts, respectively (p=0.0106). The 24-month overall survival rates were 78.4% (95% CI: 0.64-0.87) and 81.4% (95% CI: 0.75-0.86) for the RED and MAB cohorts, respectively (p=0.7461). For patients with high revised International Prognostic Index scores, 24-month PFS was 45.5% (95% CI: 0.17-0.71) and 63% (95% CI: 0.37-0.80) for the RED and MAB cohorts, respectively (p=0.0711). In the RED cohort, central nervous system (CNS) relapse was significantly increased compared to the MAB cohort (10% vs. 1.83%, p=0.004). Among the RED cohort, bone involvement at the time of diagnosis was a risk factor for CNS relapse (p=0.028). Thirteen patients died in follow-up. There were no serious adverse events causing the cessation of the drugs.
RED has an ORR similar to that of MAB. However, PFS rates were worse in the RED cohort. Additionally, CNS relapse ratio was a major concern for our RED cohort. Large prospective controlled studies and real-life data with longer follow-up are needed to document the non-inferiority of RED compared to MAB.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) with aggressive disease characteristics resulting in multiple relapses after initial treatment. Lenalidomide is an immunomodulatory ...agent approved in the US for patients with relapsed/refractory MCL following bortezomib based on results from 3 multicenter phase II studies (2 including relapsed/refractory aggressive NHL and 1 focusing on MCL post-bortezomib). The purpose of this report is to provide longer follow-up on the MCL-001 study (follow-ups were 6.8 NHL-002, 7.6 NHL-003, and 52.2 MCL-001 months). The 206 relapsed MCL patients treated with single-agent lenalidomide (25 mg/day PO, days 1 to 21 every 28-days) had a median age of 67 years (63% ≥65 years), 91% with stage III/IV disease, and 50% with ≥4 previous treatment regimens. With a median follow-up of X, the combined best overall response rate (ORR) was 33% (including 11% with complete remission CR/CR unconfirmed CRu). Lenalidomide produced rapid and durable responses with a median time to response of 2.2 months and median duration of response (DOR) of 16.6 months (95% CI: 11.1%-29.8%). The safety profile was consistent and manageable; myelosuppression was the most common adverse event (AE). Overall, single-agent lenalidomide showed consistent efficacy and safety in multiple phase II studies of heavily pretreated patients with relapsed/refractory MCL, including those previously treated with bortezomib.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective: In humans, 38 different critical blood type classification systems are currently recognized. They differ in frequencies in distinct populations. It is aimed to visualize ABO and Rh(D) ...groups distribution in Istanbul as having the largest community in Turkey. Method: Volunteered blood donor's data on the automation system were screened retrospectively. Blood donation acceptance criteria were based on the guidelines prepared by the Ministry of Health. ABO and Rh(D) groups were analyzed using column agglutination/gel centrifugation methods. Results: The study covered six years' data between the dates of January 2014 and December 2019, including 136,231 donors. The majority of the donors were found to have blood group A with a frequency of 41.88%(n=57,059). The second most common blood group was group O, and had a frequency of 34.92%(n=47,576). The blood group B (n=20,790;15.26%) and group AB (n=10,806;7.93%) were found to be the rare encountered blood groups. Among the Rh(D) group, 85.02% of the donors were Rh(D) positive. Conclusion: In transfusion medicine, ABO and Rh(D) groups' compatibility is mandatory. According to the monthly and or annual blood products requirement, there are some suggested quantities of blood units to be available at blood centres. Determining the frequency of blood group distribution of populations will help to coordinate the ratio of blood groups to be storaged. The Turkish genetic makeup is a fascinating mixture of European and Asian DNA, necessitates to find out the countries' specific ABO and Rh(D) groups ratio. We compared our results with the previously reported studies performed in different cities of Turkey and the world around. Thus, our research as giving the overall distribution of ABO and Rh(D) groups from the largest city of Turkey reflecting the general ethnic background of the country, would help to the establishment of a databank of ABO and Rh(D) group's ratio.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective: Peripheral T-cell lymhomas (PTCLs) represent a heterogeous group of diseases, with poor long-term outcomes excluding ALK+ anaplastic large cell lymphoma (ALCL). Method: We represent data ...of our retrospective analysis of 62 consecutive PTCL cases diagnosed since 2002. Median observation time was 16 months. Results: The overall response rate to first line treatment was 53 percent. Data related to median progression- free survival and overall survival times could not be obtained for ALK+ALCL group whereas median progression- free survival and overall survival times for ALK-negative ALCL group were 1 and 18 months, respectively. Disease progression was frequently observed histologically in ALK-negative group. For ALKnegative ALCL, advanced stage disease was defined as the presence of serum albumin <3.4 g/dl, serum total protein ≤6.2 g/dl, high serum LDH, and serum ferritin >200 ng/ml, presence of B symptoms, and extranodal involvement of more than one site. Risk factors associated with death were serum albumin <3.4 g/dl, serum total protein ≤6.2 g/dl, serum ferritin over 200 ng/ml, and bone marrow involvement at the time of diagnosis. During follow-up 39 patients (64%) died. Most common reasons were progressive disease and infections. Four patients developed secondary malignancies. Conclusion: Our study is a reflection of the ‘real-life’. Three patients died due to disease progression shortly after diagnosis without providing treatment due to aggressiveness of the disease. Alternatives to CHOP-based chemotherapies should be found for the ALK + non-anaplastic large cell lymphoma group.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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