Publications by authors named "Aaron Polliack"

184 Publications

Comparison of ibrutinib and idelalisib plus rituximab in real-life relapsed/resistant chronic lymphocytic leukemia cases.

Eur J Haematol 2021 Apr 28;106(4):493-499. Epub 2021 Jan 28.

Biothecnology Research Unit, AO of Cosenza, Cosenza, Italy.

Objectives: To compare the capacity of ibrutinib (IB) and idelalisib-rituximab (IDELA-R) of prolonging overall survival (OS) as in CLL patients, previously treated with chemotherapy only.

Methods: A real-life cohort of 675 cases has been identified and investigated in the database of the groups participating in the study.

Results: At an unadjusted univariate analysis, a significant death risk reduction was observed favoring IB (IDELA-R vs IB HR = 0.5, 95% CI = 0.36-0.71) although with some limitations due to the non-randomized and retrospective nature of the study and to the lower number of patients in the IDELA-R group (112 cases) related to the current prescribing practice. To overcome the potential problem of confounding by indication, we adjusted the association between the type of therapy and mortality for all variables significantly associated with OS at Cox univariate analysis. Furthermore, those variables, differently distributed between the two study groups, were introduced into the multivariate Cox model to improve the effectiveness of the analysis. By introducing all these variables into the multiple Cox regression model, we confirmed the protective effect of IB vs IDELA-R (HR = 0.67, 95% CI = 0.45-0.98, P = .04) independent of potential confounders.

Conclusions: Although our analysis presents some constraints, that is, the unavailability of additional potential confounders, and the retrospective nature of the study, this observation may be of help for the daily clinical practice, particularly in the absence of randomized trials comparing the two schedules.
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http://dx.doi.org/10.1111/ejh.13573DOI Listing
April 2021

Chronic lymphoproliferative disorders and secondary cancers in the era of purine analogues and beyond.

Leuk Lymphoma 2021 Apr 22;62(4):771-778. Epub 2020 Nov 22.

Peter MacCallum Cancer Centre, Melbourne, Australia.

The low grade chronic lymphoproliferative disorders include chronic lymphocytic leukemia, Waldenstroms macroglobulinemia, follicular lymphoma and hairy cell leukemia. Traditionally considered incurable, these disorders have been associated with a risk of haematological and solid organ malignancies secondary to both the underlying disease and the associated treatment. The introduction of purine analogues into treatment paradigms has seen increased rates of therapy related myelodysplasia reported and it remains unclear yet on the impact the targeted novel therapies play in the development of secondary cancers. We review the rates of secondary malignancy in the chronic lymphoproliferative disorders with a particular focus on the role of the purine analogues in the development of therapy related MDS.
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http://dx.doi.org/10.1080/10428194.2020.1849682DOI Listing
April 2021

Demyelinating brain lesions developing in a patient with chronic lymphocytic leukemia shortly after treatment with a fludarabine containing regimen.

Hematol Oncol 2021 Feb 1;39(1):129-133. Epub 2020 Nov 1.

Haematology Unit, Bnai-Zion Medical Centre, Haifa, Israel.

Autoimmune manifestations are known to occur in patients with chronic lymphocytic leukemia (CLL) and of these hemolytic anemia and immune thrombocytopenia are the most well recognized. Autoimmunity may also be triggered by some of the therapeutic agents used like purine analoges and these events may sometimes be severe and even fatal. Non-hematological autoimmune stigmata occur far less frequently and are rarely encountered. Here we report a 59 year-old-woman, with CLL, who complained of recurrent headache starting 1 month after completing 6 cycles of fludarabine, cyclophosphamide, and rituximab combination therapy. Computed tomography scan of the brain showed a contrast enhancing lesion of 1 cm in diameter, with surrounding edema in the right frontal lobe. Brain MRI revealed ring enhancing lesions in the right frontal lobe and some additional small lesions in the left parietal lobe. Brain biopsy showed an inflammatory demyelinating lesion, not associated with JC virus. The patient subsequently improved after steroid therapy. Currently, after 2 years of follow-up, she remains in complete hematologic remission, has no neurological deficits, and is carefully followed by a team of neurologists and hematologists. Treating physicians should be aware of this rare autoimmune inflammatory demyelinating lesion which can occur in patients with CLL during the course of treatment and that may be linked to treatment with purine analogues like fludarabine.
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http://dx.doi.org/10.1002/hon.2815DOI Listing
February 2021

Bone lesions in hairy cell leukemia: Diagnosis and treatment.

Eur J Haematol 2020 Dec 19;105(6):682-691. Epub 2020 Aug 19.

Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland.

Skeletal involvement is a rare complication of hairy cell leukemia (HCL) with an incidence of approximately 3%. Bone lesions are commonly lytic, and the most common sites of involvement are the femoral head and neck. Skeletal involvement is typically associated with high tumor burden and bone marrow infiltration. However, isolated cases of skeletal disease without splenomegaly or bone marrow involvement are occasionally reported. This review focuses on skeletal lesions in HCL, particularly the pathogenesis, clinical symptoms, diagnostic methods, and treatment approach. A literature review of the MEDLINE database for articles in English concerning hairy cell leukemia, skeletal symptoms, bone involvement was conducted via PubMed. Publications from January 1970 to May 2020 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles.
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http://dx.doi.org/10.1111/ejh.13505DOI Listing
December 2020

Multifocal osteolytic lesions in hairy cell leukemia-the importance of PET/CT in diagnosis and assessment.

Ann Hematol 2020 Jun 12. Epub 2020 Jun 12.

Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Ul. Ciolkowskiego 2, Lodz, Poland.

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http://dx.doi.org/10.1007/s00277-020-04121-3DOI Listing
June 2020

Improving the international prognostic index score using peripheral blood counts: Results of a large multicenter study involving 520 patients with diffuse large B cell lymphoma.

Hematol Oncol 2020 Oct 17;38(4):439-445. Epub 2020 Jun 17.

Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italy.

The main purpose of this study was to assess whether it is possible to improve the prognostic impact of international prognostic index (IPI) score by combining it with peripheral blood counts. Thus, we evaluated the prognostic power of lymphocyte, neutrophil, and monocyte counts in 520 patients with diffuse large B cell lymphoma treated with R-CHOP, confirming that these parameters have a strong impact on overall survival (OS). Using revised IPI (R-IPI), 44% of patients were categorized as poor-risk and showed an OS at 5 years of 46%. As OS at 5 years of the 520 patients is 67%, it is clearly evident that R-IPI tends to overestimate the proportion of patients with poor prognosis. Accordingly, in an attempt to improve the discriminating power of R-IPI, we evaluated and compared three different scores by combining the neutrophil lymphocyte ratio (NLR) and absolute monocyte count (AMC) with the following values: (a) IPI score 3-5, (b) age > 60 years and performance status, (c) age  ≥ 65 years and LDH > ULN. The three indexes studied, had a similar 5 years OS for the high-risk group (46%-52%), but the proportion of patients classified as poor-risk were 37%, 20%, and 32%, respectively, which are lower than 44% identified with R-IPI. Thus, while R-IPI overestimates the number of high-risk patients, after applying our models, it is possible to recognize patients who are truly at high-risk. Of the three scores, the most accurate appears to be that based on NLR, AMC, LDH > ULN and age ≥ 65 years, which identifies 32% of high-risk patients, correlating well with what is seen in clinical practice.
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http://dx.doi.org/10.1002/hon.2757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687198PMC
October 2020

Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group.

Am J Hematol 2020 06 14;95(6):604-611. Epub 2020 Mar 14.

Division of Experimental Oncology, IRCCS Ospedale San Raffaele, Milan, Italy.

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.
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http://dx.doi.org/10.1002/ajh.25766DOI Listing
June 2020

The challenge of unavailable IGH mutational status in CLL in resource-limited settings.

Leuk Lymphoma 2020 06 24;61(6):1275-1276. Epub 2020 Feb 24.

Department of Hematology, Hadassah - Hebrew University Medical Center, Jeruslaem, Israel.

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http://dx.doi.org/10.1080/10428194.2020.1731502DOI Listing
June 2020

Ibrutinib in the treatment of chronic lymphocytic leukemia: 5 years on.

Hematol Oncol 2020 Apr 10;38(2):129-136. Epub 2019 Dec 10.

Department of Hematology, Hadassah-Hebrew-University Medical Center, Jerusalem, Israel.

A major revolution in the treatment of chronic lymphocytic leukemia (CLL) began with the approval of ibrutinib, a first-in-class oral inhibitor of Bruton tyrosine kinase (BTK), for the treatment of relapsed/refractory (R/R) and/or TP53 mutated patients with CLL. However, 5 years later, some issues relating to this disorder still remain including the fact that with ibrutinib only a relatively small proportion of patients achieve complete remission and that ibrutinib-resistant CLL clones can develop in about 20% of patients. In addition, therapy must still be given continuously, and toxicities leading to drug discontinuation occur in about 30% of patients. In the meantime second-generation BTK inhibitors have already aroused considerable interest and gathered momentum. A possible strategy to overcome some of these obstacles is to combine ibrutinib with other targeted agents especially in high-risk disease, such as previously treated refractory patients or those with TP53 aberrations or complex karyotypes, in whom rapid eradication of disease is most desirable. Therapy with single agent ibrutinib should be part of a sequential approach for patients with low risk disease, especially in older patients (aged >70 years) with a higher burden of comorbidities. Long-term results of ongoing studies combining Ibrutinib with (chemo)-immunotherapy or other targeted agents are eagerly awaited. Future clinical trials are indeed still needed to provide answers to these open questions.
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http://dx.doi.org/10.1002/hon.2695DOI Listing
April 2020

Report of the International Splenic Lymphoma Study Group meeting held in 2019 in Barcelona, Spain.

Leuk Lymphoma 2020 02 15;61(2):285-287. Epub 2019 Oct 15.

Institut D'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Hospital Clinic, Barcelona, Spain.

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http://dx.doi.org/10.1080/10428194.2019.1675878DOI Listing
February 2020

A new risk model to predict time to first treatment in chronic lymphocytic leukemia based on heavy chain immunoparesis and summated free light chain.

Eur J Haematol 2019 Oct 26;103(4):335-341. Epub 2019 Jul 26.

The Binding Site Group Ltd, Birmingham, UK.

Background: Chronic lymphocytic leukemia (CLL) is frequently accompanied by immune dysregulation.

Aims: In this multicenter prospective study, we investigated whether heavy + light chains (HLC: IgGκ, IgGλ, IgAκ, IgAκ, IgMκ, IgMλ) and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) could be used as novel prognostic markers of immunoparesis in 105 treatment-naïve patients with CLL.

Results: Heavy + light chains immunoparesis of ≥1, ≥2, and ≥3 isotypes was evident in 74 (70%), 58 (55%), and 36 (34%) patients, respectively. Severe HLC immunoparesis was identified in 40 (38%) patients. Of the IgG subclasses, IgG1 and IgG2 were most frequently suppressed, affecting 46 (44%) and 36 (34%) patients, respectively; 63 (60%) patients had low levels of at least one IgG subclass. In multivariate analysis, severe HLC immunoparesis (hazard ratio [HR]: 36.5; P = .010) and ΣFLC ≥ 70 mg/L (HR: 13.2; P = .004) were the only factors independently associated with time to first treatment (TTFT). A risk model including these variables identified patients with 0, 1, and 2 risk factors and significantly different TTFT (P < .001). Patients with two factors represented an ultra-high-risk group with a median TTFT of only 1.3 months.

Conclusion: The above findings demonstrate the potential for the use of HLC immunoparesis, together with sFLC measurements, as future prognostic biomarkers in CLL.
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http://dx.doi.org/10.1111/ejh.13288DOI Listing
October 2019

Primary peg-filgrastim prophylaxis versus filgrastim given "on demand" for neutropenia during therapy with cladribine for hairy cell leukemia.

Leuk Res 2019 07 19;82:24-28. Epub 2019 May 19.

Department of Hematology, Hadassah Hebrew University Medical center, Jerusalem, Israel.

Background: Major advances in the treatment of patients with hairy cell leukemia (HCL) have been made following the introduction of purine analogues. The major significant short-term toxicity of cladribine therapy are neutropenia and neutropenic fever (NF) which may be life-threatening.

Aim: In this retrospective study, we compared the incidence and duration of neutropenia and hospitalization in patients with HCL treated with cladribine followed by peg-filgrastim as primary prophylaxis versus daily filgrastim given "on demand" according to absolute neutrophil count (ANC).

Methods: Medical records of patients with HCL diagnosed and followed in 12 medical centers in Israel during 1985-2015 were examined for details of disease at diagnosis. The efficacy of peg-filgrastim and filgrastim was assessed by evaluating the incidence of neutropenia (ANC < 1.0 × 10 [9]/L), number and length of hospitalizations, and number of days from the last day of therapy to recovery of ANC to >1.0 × 10 [9]/L.

Results: The study population included 202 patients with HCL, 159 of whom (80.7%) were treated with cladribine; 78 patients (49%) required hospitalization for the administration of broad-spectrum antibiotics due to NF. Twenty-eight (19%) patients were treated with peg-filgrastim as primary prophylaxis, while 74 (64%) received filgrastim "on demand" due to neutropenia. Median length of hospitalization, and nadir duration were 8 and 18 days respectively (p = 0.71, p = 0.44).

Conclusions: Infectious complications post-cladribine treatment remain high. No difference was found in terms of incidence of NF, number of febrile days, and nadir duration in patients receiving primary peg-filgrastim prophylaxis compared to filgrastim given on demand. Both approaches are justifiable, and the choice remains at the physician's discretion.
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http://dx.doi.org/10.1016/j.leukres.2019.05.006DOI Listing
July 2019

Five Ibrutinib-Associated Side Effects That All Clinicians Should Be Aware of.

Acta Haematol 2019 9;141(4):254-255. Epub 2019 Apr 9.

Hematology Unit, Bnai Zion Medical Center, Haifa, Israel,

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http://dx.doi.org/10.1159/000497356DOI Listing
October 2019

Low-dose fludarabine and cyclophosphamide combined with standard dose rituximab (LD-FCR) is an effective and safe regimen for elderly untreated patients with chronic lymphocytic leukemia: The Israeli CLL study group experience.

Hematol Oncol 2019 Apr 12;37(2):185-192. Epub 2019 Mar 12.

Department of Hematology, Hadassah University Hospital and Hebrew University Medical School, Jerusalem, Israel.

Chronic lymphocytic leukemia (CLL) is a disease of elderly patients. The fludarabine, cyclophosphamide, and rituximab (FCR) regimen is considered the treatment of choice for young fit patients with CLL; however, this combination is toxic for older patients. At the time this study was first planned and initiated, there was no standard chemo-immunotherapy regimen regarded as standard therapy for the less fit elderly patient with CLL. Here, we conducted a single-arm, phase II trial to examine the efficacy and safety of lower-dose fludarabine and cyclophosphamide combined with a standard dose of rituximab (LD-FCR) in elderly patients with previously untreated CLL. Forty patients received LD-FCR and were included in the efficacy analysis. Two patients treated with FC alone were only included in the safety analysis. The median age was 72.7 years (range, 65.0 to 85.0). The overall response and complete response rates were 67.5% and 42.5%, respectively. Median progression-free survival (PFS) was 35.5 months (95% CI, 29.27-41.67). Two patients (4.8%) died during the study period. Hematological toxicities and infections were the most common complications encountered; grade 3 to 4 treatment-related neutropenia occurred in 20 (47.6%) patients. During the entire study follow-up, 26 patients (61.9%) had all grades of infection including six (14.3%) with neutropenic fever and eight (19%) with grade 3 to 4 non-neutropenic infections. In conclusion, LD-FCR is an effective and relatively safe regimen for previously untreated patients with CLL. It has the advantage of being both "time and cost limited" and, even in the era of novel agents, can still be considered when planning treatment for elderly patients without high-risk biomarkers. However, recent results in fit elderly patients using the combination of bendamustine and rituximab which have achieved longer PFS with good safety profile must be taken into consideration in this regard.
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http://dx.doi.org/10.1002/hon.2580DOI Listing
April 2019

CLL and CML sometimes meet and circulate together.

Leuk Lymphoma 2019 06 24;60(6):1352-1353. Epub 2019 Jan 24.

b Department of Hematology, Hadassah -Hebrew University Medical Center , Jerusalem , Israel.

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http://dx.doi.org/10.1080/10428194.2018.1564050DOI Listing
June 2019

Systemic lupus erythematosus and lymphoma: Incidence, pathogenesis and biology.

Leuk Res 2018 12 12;75:45-49. Epub 2018 Nov 12.

Medicine A, Rabin Medical Center, Petah-Tikva, Israel; Institute of Hematology, Davidoff Cancer Center, Israel; Sackler School of Medicine, Tel-Aviv, Israel. Electronic address:

Systemic Lupus Erythematosus (SLE), a well recognized systemic autoimmune disease is associated with an increased risk of malignancies, particularly lymphoma. Various studies have shown this risk to be as high as 4-7-fold compared to the general population. The pathogenesis of lymphoma in patients with SLE is still not well understood. In this review we summarize the world literature and update current knowledge on the interesting link between SLE and lymphomagenesis. We relate in turn to incidence rates of lymphoma in SLE and subtypes of lymphoma encountered; pathogenesis and relevant theories proposed; links with EBV and the possible role of continued activity of lupus and of immunosuppressive therapy in lymphomagenesis. It is clearly evident that further studies are needed to improve the understanding of this association. Some cytokines and proteins associated with cell survival and proliferation, such as BAFF, APRIL, IL6 and BCL2, have been found to be elevated both in SLE and lymphoma. These factors may well impact pathogenesis, however, a direct "cause and effect" relationship is yet to be demonstrated.
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http://dx.doi.org/10.1016/j.leukres.2018.11.004DOI Listing
December 2018

Hairy Cell Leukemia: Retrospective Analysis of Demographic Data and Outcome of 203 Patients from 12 Medical Centers in Israel.

Anticancer Res 2018 Nov;38(11):6423-6429

The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

Background/aim: In this retrospective study, we summarized the national Israeli experience with hairy cell leukemia (HCL) in a large cohort of patients with a long follow-up.

Patients And Methods: Demographic data, and relevant laboratory and clinical parameters were analyzed, emphasizing the outcome after first-line treatment with cladribine.

Results: Data on 203 patients was collected from 12 medical centers during 1985-2015. Mean and median follow-up were 7.5 years and 5.18 years (interquartile range=0.1-40 years), and 5- and 10-year survival were 96% and 90.62%, respectively. The median age of diagnosis was 55.5 years for Jews and 49 years for Arabs (p=0.021), and most patients were males (81.77%); 52.2% were Ashkenazi Jews, 36.1% Sephardic Jews and 11.7% were Arab, Druze or other ethnicity. Cladribine was given to 159 patients (80.7%%) and most (62%) received intravenous (i.v.) and 38% received subcutaneous (s.c.) therapy. Overall survival and time to next treatment were not significantly different between the two schedules (i.v., s.c.). In univariate analysis of a variety of factors, only age >65 years had a negative impact on outcome, with shorter overall survival. It is of interest that Arab patients with HCL were diagnosed at an earlier age, but had a similar clinical course and outcome to both Ashkenazi and Sephardic Jews.
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http://dx.doi.org/10.21873/anticanres.13003DOI Listing
November 2018

The Frequency and Prognostic Value of Neutrophilia in Chronic Lymphocytic Leukemia.

Anticancer Res 2018 Aug;38(8):4731-4734

The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

Background/aim: In chronic lymphocytic leukemia (CLL) the absolute neutrophil count (ANC) has generally been reported to be within normal limits and leukocytosis is due to absolute lymphocytosis. However, other cell types such as neutrophils and monocytes may also exceed the normal range in this disorder. The aim of this retrospective study was to evaluate the frequency and prognostic value of neutrophilia defined as an ANC>7×10/l and monocytosis- an absolute monocyte count (AMC)>1×10/l in 113 patients with chronic lymphocytic leukemia (CLL).

Materials And Methods: We analyzed clinical and laboratory data from the records of patients with CLL followed in the Hematology unit of a tertiary hospital in Israel. Patients were categorized according to their ANC and AMC before treatment and their data compared.

Results: In 24 (21%) patients, neutrophilia was present at diagnosis while 40 (35%) had monocytosis. We identified that 9% of cases had neutrophilia with normal AMC. This subgroup of patients had a better prognosis with lower mortality rate, longer time-to-treatment interval and a higher rate of complete or partial response to treatment compared to patients without neutrophilia or monocytosis.

Conclusion: The presence of neutrophilia without monocytosis before treatment appears to be associated with a more favorable prognosis in CLL. These observations still need to be confirmed and validated in a larger cohort of patients.
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http://dx.doi.org/10.21873/anticanres.12780DOI Listing
August 2018

Outcomes of second-line treatment after fludarabine cyclophosphamide and rituximab in patients with chronic lymphocytic leukemia outside clinical trials.

Eur J Haematol 2018 Sep 3;101(3):399-406. Epub 2018 Aug 3.

Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Objective: To evaluate disease characteristics and long-term outcomes in patients requiring second-line treatment following fludarabine, cyclophosphamide, and rituximab (FCR), for relapsed/refractory disease (R/R), or following discontinuation due to toxicities.

Method: A retrospective analysis of 126 chronic lymphocytic leukemia patients treated with frontline FCR: 63 received second-line treatment (41 relapsed, nine refractory [SD/PD], 13 prior toxicity). Time to next treatment (TTNT) was calculated from beginning FCR to initiation of second-line therapy. Overall and event-free survival was calculated from initiation of salvage treatment (OS2/EFS2).

Results: Median follow-up for the entire cohort was 67 and 37 months from second-line therapy. TTNT < 24 months was associated with shorter OS2 and EFS2 similar to those observed with primary refractory disease (OS2 19 and 23 months; EFS2 12 and 9 months for TTNT < 24 months and SD/PD, respectively). TTNT ≥ 24 months (71% chemotherapy-based second-line), had longer OS2 and EFS2 (48 and 20 months). Among the 13 patients receiving second-line therapy after discontinuing FCR due to toxicity EFS2 was 41 months (59 months from initiation of FCR).

Conclusion: With limitations of sample size and treatment heterogeneity, patients progressing <24 months following FCR have poor outcomes, similar to refractory patients, while longer remissions are indicative of a chemoimmunotherapy sensitive disease. Patients who discontinue FCR for toxicities may achieve excellent outcomes with subsequent treatment.
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http://dx.doi.org/10.1111/ejh.13129DOI Listing
September 2018

Hodgkin lymphoma of the gastrointestinal tract in patients with inflammatory bowel disease: Portrait of a rare clinical entity.

Leuk Res 2018 08 17;71:1-5. Epub 2018 Jun 17.

Departments of Hematology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Patients with inflammatory bowel disease (IBD) on immunosuppression are at risk of developing lymphoma, particularly primary gastrointestinal (GI) tract non-Hodgkin lymphoma. Primary GI Hodgkin lymphoma (HL) in this setting, however, is rare and poorly defined. Here we review the available literature and also report a patient with Crohn's disease (CD) who developed GI HL. Our search yielded 12 single case studies and 7 case series involving 22 patients published between 1978-2016. Twenty-one (91%) patients had CD, and 2 had ulcerative colitis. The median age at lymphoma diagnosis was 39 years, and 18 (78%) patients were males. HL was diagnosed at a median of 8 years after IBD detection and 2 years after commencing immunosuppression. HL had a predilection (80%) to involve the inflamed GI site and the histological subtype was mixed cellularity in 65% of cases. In-situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was positive in all documented cases. HL was diagnosed in stages I, II, IV in 35%, 20% and 45% of the patients, respectively. Notably, 66% of patients with advanced disease had liver involvement. Immunosuppression was stopped in most (69%) patients at HL diagnosis. Treatment used was either chemotherapy only, surgery followed by chemotherapy, or surgery alone in 50%, 33% and 16% of cases, respectively. Four patients had an IBD flare during HL remission. Patients with IBD who develop GI HL have distinct characteristics; male sex, predominance of CD, preference to develop in inflamed sites, mixed cellularity histology, EBV positivity, and a unique spread to the liver pattern.
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http://dx.doi.org/10.1016/j.leukres.2018.06.008DOI Listing
August 2018

Rheumatoid arthritis and lymphoma: Incidence, pathogenesis, biology, and outcome.

Hematol Oncol 2018 Dec 3;36(5):733-739. Epub 2018 Jun 3.

Medicine A, Rabin Medical Center, Petah-Tikva, Israel.

Patients with rheumatoid arthritis (RA) have a greater risk of developing both Hodgkin lymphoma (HL) and non-HL than the general population. Non-Hodgkin lymphoma is more common than HL in these patients, and diffuse large B cell lymphoma is the most frequent subtype observed. Although the clinical course of lymphoma in RA is often aggressive, the prognosis in these cases is similar to that of lymphoma in the general population. In this review, we summarize data derived from both retrospective and prospective studies, regarding incidence, pathogenesis, and outcome of lymphomas in RA patients and outline the possible mechanisms and hypotheses linking these 2 disorders. Over the years, 3 main theories have been suggested to explain this association. These hypotheses relate to genetic predisposition, persistence of long standing disease activity with continued immune stimulation, and the role of anti-RA therapy given. A common genetic predisposition linking RA and lymphoma has not been established. As for treatment of RA, this includes immunosuppressive antitumor necrosis factor drugs or conventional disease modifying antirheumatic drugs like methotrexate. Neither of these drug categories appears to be associated with a higher risk of lymphoma in RA. The impact of continuing disease activity and immune stimulation appears to be the most significant in lymphomagenesis in these patients.
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http://dx.doi.org/10.1002/hon.2525DOI Listing
December 2018

Primary plasma cell leukemia in the era of novel agents for myeloma - a multicenter retrospective analysis of outcome.

Leuk Res 2018 05 2;68:9-14. Epub 2018 Mar 2.

Department of Hematology, Hadassah Medical Centre, Jerusalem, Israel.

Primary plasma cell leukemia (PPCL) is a rare form of multiple myeloma with a dismal prognosis. This retrospective multi-center study examines the national experience of PPCL in the era of novel agents. During 2002-2016, thirty-nine patients with PPCL were identified in 11 Israeli centers. One-fifth of them died in the first 2 months after diagnosis. The overall survival (OS) of those who survived the first 3 months was 22.5 months. About 70% of patients received at least one type of immunomodulatory drug (IMiD) and similarly proteasome inhibitor (PI) during treatment. There was a survival advantage for those who received IMiD but not for those who received PI or other type of standard dose chemotherapy. In multivariate analysis, low performance status and increased uric acid were also associated with shorter OS. In conclusion, this study demonstrates favorable impact of treatment with IMiDs and hematopoietic cell transplantation on the survival of PPCL patients.
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http://dx.doi.org/10.1016/j.leukres.2018.02.010DOI Listing
May 2018

Amegakaryocytic Thrombocytopenia and Subsequent Aplastic Anemia Associated with Apparent Epstein-Barr Virus Infection.

Acta Haematol 2018;139(1):7-11. Epub 2018 Jan 5.

Internal Medicine B Department, Bnai Zion Medical Center, Haifa, Israel.

Acquired amegakaryocytic thrombocytopenia (AAT), a rare entity characterized by severe thrombocytopenia and the absence of megakaryocytes in the bone marrow, may mimic or precede the diagnosis of aplastic anemia (AA). Here, we describe a patient who presented with apparent Epstein-Barr virus (EBV)-associated immune thrombocytopenia resistant to several lines of therapies, which was in fact a form of AAT with some features of AA. He eventually responded to therapy with eltrombopag, cyclosporine A (CSA), and antithymocyte globulin (ATG) and recovered completely. EBV infection is known to cause a variety of benign and malignant hematologic disorders, including bone marrow failure. However, to the best of our knowledge, this is the first case report of EBV-associated AAT. Treatment options for AAT are still not well defined, and even response to eltrombopag together with CSA and ATG does not always imply successful therapy. The natural history of EBV infection may well be sufficient to explain unexpected eventual recovery.
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http://dx.doi.org/10.1159/000484595DOI Listing
March 2019

Chronic lymphocytic leukemia is becoming more complex: how to define complex karyotype?

Leuk Lymphoma 2018 03 18;59(3):521-522. Epub 2017 Sep 18.

a Hematology Unit , Bnai Zion Medical Center , Haifa , Israel.

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http://dx.doi.org/10.1080/10428194.2017.1376748DOI Listing
March 2018