Current Status and Management of Chronic Myeloid Leukemia in the Gulf Region: Survey Results and Expert Opinion.

Studies on chronic myeloid leukemia (CML) in the Gulf region are scarce, consisting of a survey and expert meeting that included 15 experts in 2023 which discussed CML diagnosis, testing, treatment objectives, toxicities, and discontinuation in the Gulf region. Most patients were reported to be in first-line therapy, and the most common treatments were imatinib/imatinib generic in first-line and dasatinib in second- and third-lines. Mutation analysis was not reported to be routinely performed at the time of diagnosis but rather in case of progression to accelerated/blast phase or any sign of loss of response. While all participants were aware that BCR-ABL should be monitored every three months during the first year of treatment, 10% reported monitoring BCR-ABL every six months in practice due to test cost and lab capability. The most important first-line therapy objective was "achievement of major molecular response" (MMR) in younger patients and "overall survival" in older ones. The most important treatment objectives were "MMR" and "early molecular response followed by prolongation of overall survival" in the short term and "treatment-free remission" in the long term. The current practices in CML in the Gulf region appear to be similar to global figures.

Immune reconstitution and survival, following hematopoietic stem cell transplantation in Omani patients with inborn errors of immunity.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for certain inborn errors of immunity. METHODS: A 17-year retrospective cohort study was conducted on 40 immunodeficient patients who underwent HSCT. RESULTS: The median age at transplant was 11.0 months (4.6-61.0). Donors were primarily matched sibling donors (60%). 90% and 85% of patients received conditioning and graft-versus-host disease (GVHD) prophylaxis, respectively. The mean donor chimerism at the last follow-up was 88.6% ± 17.9% (40-100). Median serum immunoglobulin (Ig) G level, CD4+ T-cell count, and CD19+ B-cell count were 11.7 g/L (9.2-13.6), 0.9 × 109/L 0.6-1.2), and 0.5 × 109/L (0.2-0.7), respectively. 29 patients (72.5%) received intravenous immunoglobulins (IVIG) therapy, with a median duration of 10.0 months (4.0-14.0). The median post-transplant follow-up was 6.5 years (IQR:1.4-11.5). The 10-year overall probability of survival is 84.3%. CONCLUSION: Monitoring IRC is important in ensuring adequate disease-free survival.

Chronic myeloid leukemia diagnosed in pregnancy: management and outcome of 87 patients reported to the European LeukemiaNet international registry.

The management of chronic myeloid leukemia (CML) diagnosed during pregnancy is a rare and challenging situation. We report the treatment and outcome of 87 cases diagnosed in chronic phase from 2001-2022 derived from the largest international observational registry, supported by the European LeukemiaNet (ELN), of 400 pregnancies in 299 CML women. Normal childbirth occurred in 76% without an increased rate of birth abnormalities or life-threatening events, including in patients untreated or treated with interferon-α and/or imatinib in 2nd-3rd trimester. The low birth weight rate of 12% was comparable to that seen in the normal population. Elective and spontaneous abortions occurred in 21% and 3%, respectively. The complete hematologic response rate before labor was 95% with imatinib and 47% with interferon only. No disease progression during pregnancy was observed, 28% of the patients switched their therapy at varying times after delivery. Treatment options balance the efficacy and safety for mother and infant: interferon-α can commence in the 1st trimester and continued throughout in cases of good disease control and tolerability. Because of limited placental crossing, selected tyrosine kinase inhibitors (imatinib and nilotinib) seem to be safe and effective options in 2nd and 3rd trimester while hydroxycarbamide offers few benefits.

The role of preoperative transfusion in sickle cell disease, a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to provide guidance on preoperative blood transfusion strategies for patients with sickle cell disease (SCD). We included all randomized controlled and observational studies exploring the clinical outcomes of preoperative blood transfusion among patients with SCD compared to the conservative transfusion strategy until 14/09/2022. Sixteen studies involving 3486 participants were analysed. The findings revealed a significantly higher bleeding rate in patients who received preoperative transfusion than those who followed a conservative strategy (RR = 4.32, 95% CI 1.75-10.68, P = 0.002, I2 = 0%). However, the two strategies had no significant differences in other clinical outcomes, such as acute chest syndrome, painful crisis, fever, neurological complications, thrombosis, ICU admission, and mortality. It is important to note that all the included studies had a moderate risk of bias. Preoperative transfusion in SCD was associated with a higher bleeding risk but a similar risk in other outcomes compared to conservative strategies. Notably, the increased bleeding risk observed seldom had clinical significance. We recommend individualizing management strategies, considering the overall positive impact of transfusions in reducing complications. Further high-quality studies are needed to refine recommendations.

Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs.

Midkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some human innate antigen-presenting cells (iAPCs), i.e., monocyte-derived dendritic cells (MDDCs) and macrophages stimulated through Toll-like receptor (TLR)-4, and plasmacytoid dendritic cells (pDCs) stimulated through TLR 7. While PTN production was only documented in tissue macrophages. TLRs 3, 7, 8, and 9 are nucleic acid sensing (NAS) TLRs that detect nucleic acids from cell damage and infection and induce iAPC responses. We investigated whether NAS TLRs can induce MK and PTN production by human iAPCs, namely monocytes, macrophages, MDDCs, myeloid dendritic cells (mDCs), and pDCs. Our results demonstrated for the first time that PTN is produced by all iAPCs upon TLR triggering (p < 0.01). IAPCs produced more PTN than MK (p < 0.01). NAS TLRs and iAPCs had differential abilities to induce the production of MK, which was induced in monocytes and pDCs by all NAS TLRs (p < 0.05) and in MDDCs by TLRs 7/8 (p < 0.05). TLR4 induced a stronger MK production than NAS TLRs (p ≤ 0.05). Monocytes produced higher levels of PTN after differentiation to macrophages and MDDCs (p < 0.05). The production of MK and PTN differs among iAPCs, with a higher production of PTN and a selective induction of MK production by NAS TLR. This highlights the potentially important role of iAPCs in angiogenesis, tumors, infections, and autoimmunity through the differential production of MK and PTN upon TLR triggering.

Thrombopoietin-receptor agonists for adult patients with immune thrombocytopenia: a narrative review and an approach for managing patients fasting intermittently.

Introduction: Thrombopoietin-receptor agonist (TPO-RAs) currently represent the state of art for treating immune thrombocytopenia. Their different molecular structures contribute to the difference in their pharmacodynamics and pharmacokinetics. This narrative review aims to provide an overview of the current TPO-RAs approved for primary immune thrombocytopenia (romiplostim, eltrombopag, avatrombopag) and the effect of intermittent fasting in adult patients receiving TPO-RAs. Areas covered: Literature was searched with no limits on date or language, using various combinations of keywords. Data on the pharmacokinetics, pharmacodynamics, efficacy, and safety of TPO-RAs and the effect of intermittent fasting were summarized. Expert opinion: Switching between TPO-RAs is a useful strategy to tackle some associated limitations. Romiplostim and avatrombopag have an advantage over eltrombopag as they do not require any dietary restrictions. In cases where romiplostim and avatrombopag are unavailable, patients should be educated on the appropriate administration, possible interactions, and dietary restrictions before initiating eltrombopag.

Coexistence of sickle cell disease and systemic lupus erythematosus is associated with quantitative and qualitative impairments in circulating regulatory B cells.

The incidence of connective tissue diseases such as systemic lupus erythematous (SLE), in adult patients with sickle cell disease (SCD), appears to be increasing. The exact causes underlying this increased risk are still unknown, but a link with B regulatory (Breg) cells is possible as these cells suppress inflammatory responses, and maintain tolerance. Quantitative and qualitative analyses of circulating Breg cells were performed in a cohort of SCD patients with SLE, and their levels were correlated with key soluble mediators promoting autoreactive B cells. We demonstrated that levels of Breg cells were significantly decreased in SCD patients with SLE compared to patients with SCD only or healthy controls. Functional analysis of Breg cells from SCD patients with SLE revealed impairments in IL-10 production that correlated with lower levels of STAT3 phosphorylation, without abnormal expression of IL-10 receptor on Breg cells. On the other hand, BAFF levels were substantially elevated in SCD patients with SLE, but not significantly associated with Breg cell levels. Collectively, these results indicated numerical and functional deficits of Breg cells in SCD patients with SLE and their capacity to maintain tolerance and control inflammation is imbalanced, which leads to the development of autoimmune responses.

Clinicopathological Profile of Paroxysmal Nocturnal Hemoglobinuria among Omani Patients: A Case Series.

We aimed to estimate the nature and prevalence of paroxysmal nocturnal hemoglobinuria (PNH) among Omani patients. We performed a retrospective review of all patients who were tested for PNH by flow cytometry at the Sultan Qaboos University Hospital, Muscat, between 2012 and 2019. Manifestations, treatment modalities, and outcomes were assessed. A total of 10 patients were diagnosed or were on follow-up for PNH (median age 22.5 years). Clinical manifestations included fatigue (80%) and anemia (70%). Six patients had classical PNH with hemolysis, three had PNH in the context of aplastic anemia, and one patient had subclinical PNH. The median total clone size (type II + III) for neutrophils was 95.5 (range: 1.5-97) (FLAER/CD24) and for monocytes was 91.6 (range = 0.04-99) (FLAER/CD14). Four patients had clone sizes > 50% at the time of diagnosis. The median follow-up period of the patients was 62 months (range = 8-204 months). One patient suffered thrombosis. Three patients were on immunosuppressant agents, five were initiated on eculizumab, and four had a bone marrow transplant. No deaths were reported in the cohort. The estimated average incidence of PNH among Omani patients was 1.5 per 5 000 000. PNH is rare in the Omani population. The predominant presentation is hemolytic anemia.

The Challenges in Diagnosis and Management of Acquired Thrombotic Thrombocytopenic Purpura: Consensus Report from Three Gulf Countries.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare hematological emergency characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, and multiorgan failure due to autoimmune-mediated deficiency in ADAMTS-13 activity. Currently, plasma exchange, with or without steroids, is the frontline option for the management of aTTP. The treatment should be started promptly once the disorder is clinically suspected. Besides, immunomodulators were studied in patients with aTTP to achieve stable remission and reduce the risk of relapse in patients with suboptimal response to plasma exchange; however, clinical trials showed equivocal results. Published data on early diagnosis, referral, and treatment patterns of aTTP patients in the member nations of the Arabian Gulf Cooperation Council (GCC) are still lacking. Therefore, the present consensus report aimed to present an overview of aTTP situation in GCC by bringing together a panel of experts from three GCC nations, to share their views on current trends and practices regarding aTTP. The experts discussed challenges including the lack of reliable data regarding the incidence of aTTP in GCC and delayed results of ADAMTS-13 activity testing. Limited patient access to tertiary centers and low level of awareness about the aTTP clinical spectrum among general practitioners are other challenges. The experts agreed that there is a need for national and regional consensus regarding the diagnosis and treatment of aTTP in the Gulf region.

Human macrophages and monocyte-derived dendritic cells stimulate the proliferation of endothelial cells through midkine production.

The cytokine midkine (MK) is a growth factor that is involved in different physiological processes including tissue repair, inflammation, the development of different types of cancer and the proliferation of endothelial cells. The production of MK by primary human macrophages and monocyte-derived dendritic cells (MDDCs) was never described. We investigated whether MK is produced by primary human monocytes, macrophages and MDDCs and the capacity of macrophages and MDDCs to modulate the proliferation of endothelial cells through MK production. The TLR stimulation of human monocytes, macrophages and MDDCs induced an average of ≈200-fold increase in MK mRNA and the production of an average of 78.2, 62, 179 pg/ml MK by monocytes, macrophages and MDDCs respectively (p < 0.05). MK production was supported by its detection in CD11c+ cells, CLEC4C+ cells and CD68+ cells in biopsies of human tonsils showing reactive lymphoid follicular hyperplasia. JSH-23, which selectively inhibits NF-κB activity, decreased the TLR-induced production of MK in PMBCs, macrophages and MDDCs compared to the control (p < 0.05). The inhibition of MK production by macrophages and MDDCs using anti-MK siRNA decreased the capacity of their supernatants to stimulate the proliferation of endothelial cells (p = 0.01 and 0.04 respectively). This is the first study demonstrating that the cytokine MK is produced by primary human macrophages and MDDCs upon TLR triggering, and that these cells can stimulate endothelial cell proliferation through MK production. Our results also suggest that NF-κB plays a potential role in the production of MK in macrophages and MDDCs upon TLR stimulation. The production of MK by macrophages and MDDCs and the fact that these cells can enhance the proliferation of endothelial cells by producing MK are novel immunological phenomena that have potentially important therapeutic implications.

Transplant Associated Graft versus Host Disease.

Graft versus host disease (GVHD) occurs quite often after hematopoietic cell transplantation. However, it is a rare complication after solid organ transplantation and consists of a reaction of donor-derived immune cells directed against host tissues, which is mostly seen in liver, small intestine, and pancreas transplantation. We are presenting a 54-year-old man with a long-standing history of hypertension, hypertensive nephrosclerosis, and stage V terminal chronic kidney disease, who was on a regular hemodialysis thrice weekly. He had a living kidney transplantation done abroad. On returning, he had a normal kidney function with no obvious complications. Three years later, he presented with jaundice, anorexia, diarrhea, and abdominal pain. Laboratory evaluation showed marked elevated liver enzymes, and severe pancytopenia with evidence of hepatosplenomegaly. Liver biopsy was compatible with graft-versus-host-disease and toxic hepatitis. The patient was not cooperative with the management and he traveled abroad for the 2nd opinion. Based on the clinical presentations, laboratory, radiological, and pathological findings, transplant-associated GVHD (ta-GVHD) was confirmed. Unfortunately, this patient was complicated by severe sepsis, and confounded by a lack of cooperation with the management plan, which resulted in his demise. In the presence of a highly immunocompromised state, patients presenting with transaminitis/hyperbilirubinemia, and when drug-induced liver injury is excluded, the diagnosis of ta-GVHD needs to be highly considered.

Efficiency of day 4 compared to day 6 stem cell mobilization in allogeneic stem cell donors.

BACKGROUND: Granulocyte colony stimulating factor (G-CSF) given for 4-6 days is commonly used for mobilization of allogeneic stem cell donors. The primary objective of this study is to compare the yield of stem cell mobilization, assessed using a surrogate endpoint of CD34+ cell count, between Day 4 and Day 6. STUDY DESIGN AND METHODS: In this retrospective study we included all allogeneic stem cell donors mobilized with G-CSF for 6 days from January 2003 until October 2015 in the bone marrow transplantation unit at a tertiary academic center. Of 106 donor records reviewed, 84 were with available data and selected for the study. RESULTS: We included 84 donors with median age and weight of 19 years and 60 kg respectively. The median Day 4 WBC and CD34+ cell count were 37.4 × 109/L and 54 × 106/L respectively; while the median Day 6 WBC and CD34+ cell count were 44.4 × 109/L and 86 × 106/L respectively with a statistically significant difference from Day 4 (P < 0.001). In the multivariable model, there were no significant impact of donor's age (P = 0.215), weight (P = 0.108), height (P = 0.428) and mean corpuscular volume (P = 0.263) on the difference in CD34+ cell yield. However, the donor's blood group AB predicated a significantly higher difference (P = 0.036). CONCLUSION: Six days of G-CSF mobilization achieves higher CD34+ cell count than 4 days in allogeneic stem cell donors especially in donors with blood group AB, albeit both approaches give count higher than the successful collection threshold.

Can Gestational Anemia be Alleviated with Increased Awareness of its Causes and Management Strategies? Implications for Health Care Services.

OBJECTIVES: We conducted this study to assess the risk factors of gestational anemia and evaluate the effectiveness of a culturally-tailored nutrition educational intervention on hemoglobin (Hb) status among pregnant Omani women. Newborn birthweight was used as a birth outcome. METHODS: The study was conducted in two phases. The first phase investigated the risk factors associated with gestational anemia in 206 Omani women who were 3 20 years old and had at least completed 12 weeks of gestation. A suitable sample was recruited at a tertiary teaching hospital in Muscat, Oman. Hb status was recorded, and backward linear regression was used to analyze the demographic and obstetric variables associated with Hb levels. In the second phase, a specially designed culturally-tailored nutrition educational intervention was delivered to women in the study group by trained research assistants whereas women in the control group received routine care only. The Hb levels of the pregnant women and birth weight of newborns after the intervention were evaluated in the second phase of the study. RESULTS: The prevalence of gestational anemia among 206 pregnant Omani women was 41.7%. A significant negative relationship was found between Hb and parity whereas a positive relationship was found between Hb and gestational age. The Hb level increased as the gestational age advanced (ß = 0.31, p < 0.050) and decreased as the parity increased (ß = -0.22, p < 0.050). The pre-post mean difference of Hb levels in the study group was 11.0 g/dL and in the control group was 10.7 g/dL. The difference between the pre- and post-test Hb levels for the study group was significant (t = 3.58, p = 0.001), indicating that the culturally-tailored nutrition education intervention was effective in improving the Hb level in pregnant Omani women. No significant difference was found between the study and control group with respect to birth outcomes. CONCLUSION: The prevalence of gestational anemia is high in pregnant Omani women. The use of a specially designed culturally-tailored nutrition education intervention for pregnant women supplemented with follow-up reminders can reduce the occurrence of gestational anemia. Such programs are ultimately necessary in light of the high prevalence of gestational anemia in developing countries.

Regulatory B Cells Are Functionally Impaired in Patients Having Hemophilia A With Inhibitors.

Development of inhibitors remains a major clinical complication in patients with hemophilia A receiving replacement therapy with factor VIII (FVIII). Understanding the immune mechanisms involved in the development of inhibitors can provide valuable information about pathways to human tolerance. Recent evidence indicates that B regulatory (Breg) cells play a pivotal role in controlling the production of antibodies (Abs) while promoting follicular T helper (Tfh) cells and monocytes, expressing the low-density lipoprotein receptor-related protein (LRP/CD91), which is involved in FVIII intake from the circulation. We studied circulating levels of Breg cells along with Tfh cells and the expression of LRP/CD91 on monocytes in patients with hemophilia A using 8-color flow cytometry and cell culture. Compared to healthy controls, patients with hemophilia A with inhibitors showed a severe reduction in levels of Breg cells and produced less interleukin-10 when activated via the CD40 signaling pathway. In addition, patients with hemophilia A with inhibitors exhibited an overexpression of LPR/CD91 on monocytes and normal levels of Tfh cells. Levels of Breg cells were not significantly related to LPR/CD91 although negative associations were evidenced. Collectively, these results provide new insights into the role of Breg cells and LPR/CD91 in the development of inhibitors in patients with hemophilia A.

First Cytogenetic Profile of Omani Patients with de novo Myelodysplastic Syndromes: Comparison with data from Asia, Africa, Europe and North and South America.

Clonal cytogenetic abnormalities have been reported among 30-80% of patients with myelodysplastic syndromes (MDS); however, 20-70% of patients with MDS show a normal karyotype that may nevertheless harbour a cryptic genetic alteration. Earlier reports have suggested that the distribution of specific chromosomal aberrations varies among Western and Asian countries, with geographical and ethnic differences in the frequency of specific chromosomal aberrations. This article compared the cytogenetic data of 36 adult Omani patients with MDS to previously reported data from other populations. Differences were noted between the percentages of clonal aberrations and the median age of Omani subjects at presentation in comparison to individuals of different ethnicities and from various geographical locations. To the best of the authors' knowledge, this is the first report to describe the cytogenetic data of patients with MDS from Oman.

Therapeutic drug monitoring-guided dosing of busulfan differs from weight-based dosing in hematopoietic stem cell transplant patients.

Busulfan (Bu)-based preparative regimens in hematopoietic stem cell transplantation are commonly used. Previous studies have shown that Bu at a fixed dose of 3.2mg/kg/day (FBD) given intravenously decreases variability in drug pharmacokinetics and this decreases the dependency on therapeutic drug monitoring (TDM) of Bu. We compared the Bu dose given using TDM with the FBD of 3.2mg/kg/day. Seventy-three patients with acute leukemia, myelodysplasia, chronic myeloid leukemia, thalassemia major, and sickle cell disease were included. The mean age at transplant was 15years (range 2-55years) with 57% adults. Indication for transplantation was leukemia/myelodysplastic syndrome in 46% of the patients, while the remaining 54% were transplanted for inherited blood disorders. We found that the median FBD was lower than the median TDM dose by 39mg/day with a statistically significant difference (p<0.001) even after adjusting for the weight (median total FBD of 349mg, median TDM dose of 494mg, p<0.0001). Age and underlying condition (malignant vs. nonmalignant) were the main factors affecting Bu clearance (p<0.001 and p<0.07, respectively). TDM remains an important tool for the appropriate dosing of Bu in preparative regimens of hematopoietic stem cell transplantation, especially in populations with genetic admixture.

First Implementation of Transfusion Consent Policy in Oman: Audit of compliance from a tertiary care university hospital.

OBJECTIVES: Transfusions are a common medical intervention. Discussion of the benefits, risks and alternatives with the patient is mandated by many legislations prior to planned transfusions. At the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, a written transfusion consent policy was introduced in March 2014. This was the first time such a policy was implemented in Oman. This study therefore aimed to assess adherence to this policy among different specialties within SQUH. METHODS: The medical records of patients who underwent elective transfusions between June and August 2014 were reviewed to assess the presence of transfusion consent forms. If present, the consent forms were examined for completeness of patient, physician and witness information. RESULTS: In total, the records of 446 transfused patients (299 adult and 147 paediatric patients) were assessed. Haematology patients accounted for 50% of adult patients and 71% of paediatric patients. Consent was obtained for 75% of adult and 91% of paediatric patients. The highest adherence rate was observed among adult and paediatric haematology specialists (95% and 97%, respectively). Consent forms were correctly filled out with all details provided for 51% and 52% of adult and paediatric patients, respectively. Among inadequately completed forms, the most common error was a lack of witness details (20-25%). CONCLUSION: In most cases, the pre-transfusion consent policy was successfully adhered to at SQUH. However, further work is required to ensure full compliance with the consent procedure within different specialties. Implementation of transfusion consent in other hospitals in the country is recommended.

Accuracy of Platelet Counting by Optical and Impedance Methods in Patients with Thrombocytopaenia and Microcytosis.

OBJECTIVES: Obtaining accurate platelet counts in microcytic blood samples is challenging, even with the most reliable automated haematology analysers. The CELL-DYN(™) Sapphire (Abbott Laboratories, Chicago, Illinois, USA) analyser uses both optical density and electronic impedance methods for platelet counting. This study aimed to evaluate the accuracy of optical density and electrical impedance methods in determining true platelet counts in thrombocytopaenic samples with microcytosis as defined by low mean corpuscular volume (MCV) of red blood cells. Additionally, the impact of microcytosis on platelet count accuracy was evaluated. METHODS: This study was carried out between February and December 2014 at the Haematology Laboratory of the Sultan Qaboos University Hospital in Muscat, Oman. Blood samples were collected and analysed from 189 patients with thrombocytopaenia and MCV values of <76 femtolitres. Platelet counts were tested using both optical and impedance methods. Stained peripheral blood films for each sample were then reviewed as a reference method to confirm platelet counts. RESULTS: The platelet counts estimated by the impedance method were on average 30% higher than those estimated by the optical method (P <0.001). The estimated intraclass correlation coefficient was 0.52 (95% confidence interval: 0.41-0.62), indicating moderate reliability between the methods. The degree of agreement between methods ranged from -85.5 to 24.3 with an estimated bias of -30, suggesting that these methods generate different platelet results. CONCLUSION: The impedance method significantly overestimated platelet counts in microcytic and thrombocytopaenic blood samples. Further attention is therefore needed to improve the accuracy of platelet counts, particularly for patients with conditions associated with microcytosis.

Biclonal Gammopathy in Chronic Lymphocytic Leukemia: Case Report and Review of the Literature.

Monoclonal gammopathies are frequently seen in B-cell malignancies. Monoclonal proteins are seen in a significant proportion of patients with chronic lymphocytic leukemia (CLL), which is a clonal disorder of mature B cells. The use of more sensitive laboratory methods has enabled the detection of monoclonal proteins or light chains in the serum and/or urine in the majority of these patients. The presence of some of these monoclonal proteins may explain the different autoimmune phenomena that are associated with this disease. Some reports indicate that the finding of monoclonal proteins has a negative impact on patients' survival. The presence of two different monoclonal proteins (i.e. biclonal gammopathy) is on the other hand rare. Most of the reported cases in the literature are of patients with plasma cell disorders. In this report, we describe a rare occurrence of biclonal gammopathy in a patient with CLL. Serum protein electrophoresis and immunofixation, which were negative at the time of initial diagnosis, showed biclonal immunoglobin A (IgA) kappa and IgA lambda during the course of the disease. The patient's disease showed steady progression, despite multiple treatments. Although this could just be the result of using more sensitive laboratory techniques, biclonal gammopathy in this patient likely reflects the evolution of another clone, which would explain the encountered resistance to therapy. Because of paucity of reports, the impact of biclonal gammopathies in such patients is not known and an effort to collectively report the presentation and outcome of these patients is needed to further understand the pathophysiology and clinical significance of such a finding.