Tyrosine kinas inhibitors (TKIs) are the standard-ofcare treatment for CML. TKI-related renal adverse events (AEs) are rare and not well understood.
Here we report the case of a patient with ...proteinuria and acute kidney injury after nilotinib and a series of events.
This is a case report of a patient diagnosed with chronic-phase CML in late 2021 on follow-up at Dar El-Salam Oncology Center.
A 22-year-old male patient was diagnosed with chronic phase CML in 2021, based on quantitative polymerase chain reaction analysis for BCR-ABL1 p210 transcript (e13/e14 a2), which was expressed in amplified RNA extract at 728.55% IS. The patient was started on imatinib 400 mg/d and after 6 months, BCR-ABL1 p210 was 12.8% IS. Consequently, the treatment was declared a failure and the patient was shifted to nilotinib. A month after treatment, he developed grade III lower limb edema, scrotal edema, and proteinuria (1350 g/24h, range 42-225). Antinuclear and antimitochondrial antibody tests were negative and C3 and C4 were within normal range. Albumin/creatinine ratio was 7099.21 mg/g of creatinine (clinical albuminuria: >300). Both of the patient's kidneys were of average size, with increased cortical echogenicity (grade I). There were no gross stones or changes in back pressure.
Renal biopsy was negative for Congo red staining (no amyloid deposits). There were no kappa, lambda, C3, or immunoglobulin A or immunoglobulin G deposits. Biopsy also revealed minimal change as a result of the CML, and nephrotic syndrome. Nilotinib was discontinued and the patient was commenced on corticosteroids, diuretics, statins, and apixaban.
The patient's symptoms improved; however, on re-evaluation of CML, bone marrow aspirate showed 74% blast cells and flow cytometry was positive for CD34, CD33, HLA-DR, CD117, myeloperoxidase, and CD13. These findings suggested myeloblastic crisis; BCR-ABL1 was 42% IS.
The patient achieved complete remission after standard induction chemotherapy in combination with dasatinib.
TKI-related renal AEs are uncommon; they are usually observed in case reports and most of them have been associated with dasatinib. TKIs tend to induce fluid retention. Recently a nilotinibinduced acute interstitial nephritis has been reported. TKI-induced nephropathy is a topic worthy of further investigation.
Background: Castleman disease (CD) is a rare disorder that affects lymph nodes and has a wide range of associated symptoms. The affected lymph nodes show characteristic histological picture. Most of ...the unicentric Castleman disease (UCD) cases can be cured by complete surgical removal or radiotherapy, while multicentric CD (MCD) is much more complicated and have several subtypes and requires more effort to reach a precise diagnosis and management. Case presentation: A 17-years old female presented with sever fatigue and abdominal pain. Massive mediastinal lymphadenopathy was detected on radiological studies. Pathology confirmed a plasma cell variant of MCD. Autoimmune disorders, overlapping IgG4-related disease, TAFRO (Thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) syndrome and other malignancies were excluded after a series of investigations. She was HIV-negative, and the human herpes virus-8 status was unknown. The final diagnosis of idiopathic MCD-not otherwise specified (iMCD-NOS) was reached. She showed a very good response to corticosteroids and monoclonal antibody course of treatment. Radiological investigations showed marked regression of the lymph node mass, and there was complete resolution of her symptoms and normalization of the hematological and biochemical parameters. Conclusion: The diagnosis and management of MCD remain very challenging, and the exclusion of infectious, autoimmune, and neoplastic disorders is necessary.
There are very few reports of the coexistence of acute myeloid leukemia (AML) and breast cancer since 1965. Usually, this double malignancy carries poor prognosis; it is different from ...therapy-related (t-AML) where the cancer occurs secondary to chemotherapy.
Here we present a case of double malignancy: hematological and solid neoplasms in a female patient.
This is a case report of a patient diagnosed with AML at Mansoura Student Hospital who went to Dar El-Salam Cancer Center for further management.
A female patient 55-years old, with no significant medical history, complained of persistent fatigue; blood work up revealed leukocytosis (TLC 137×109/L), thrombocytopenia (PLT 16×109/L) and normocytic anemia (Hb 9.3 g/dL). Bone marrow (BM) examination was normocellular with 26% blasts, a picture of acute leukemia.
On completing diagnostic workup, radiological assessment discovered a left breast suspicious lesion, supra- and infra-diaphragmatic lymphadenopathy and splenomegaly with multiple focal lesions. Combined bilateral mammogram revealed left breast upper outer quadrant malignant looking mass (BIRADS 6) and right breast 3 o'clock indeterminate nodule (BIRADS 2) as well as malignant-looking bilateral axillary and supraclavicular lymph nodes. Tru-cut biopsy from left breast mass showed invasive carcinoma with signet ring features, Grade II, ER and PR positive and Her2 negative, and KI 67, 15%. No metastasis was detected. The patient went to Dar El-Salam Cancer Center for further assessment and treatment. BM biopsy specimen revision illustrated hypercellular BM, normal count and morphology of erythrocyte lineage, depressed granulocytic and megakaryocytic lineages, and infiltrated by myeloblasts, monoblasts, promonocytes and increased basophils (AML-M4). Immunophenotyping revealed positive MPO, CD13, CD33, CD117, CD 64, CD11b, CD11c, HLADR and dim CD4; t(8;21) and Inv (16) were negative. The decision was to start standard intensified chemotherapy (3+7) protocol plus neoadjuvant treatment (aromatase inhibitor).
The patient did not achieve response to induction therapy: her BM aspirate showed 49% blasts. The patient received salvage chemotherapy (high-dose cytarabine and mitoxantrone - HAM).
Synchronous occurrence of these 2 neoplasms is rarely reported. Collaboration of various expertise in the field of hematology and oncology is needed to deliver the best care for this patient.
Summary
Background
The Wnt pathway is aberrantly activated in chronic lymphocytic leukemia (CLL) and contributes to the antiapoptotic and mitogenic characteristics of CLL cells. Lymphoid ...enhancer-binding factor‑1 (LEF1) acts as a mediator and key transcription factor of the Wnt/β-catenin pathway. LEF1 helps to regulate important genes involved in tumor cell death mechanisms.
Objective
To analyze the expression levels of Wnt signaling pathway member (WNT3) and its key mediator LEF1 in Egyptian CLL patients and to detect the potential use of these genes as markers of CLL outcome.
Methods
We quantified the expression levels of Wnt3 and LEF1 in peripheral blood mononuclear cells of 30 untreated CLL and 19 healthy controls by qRT-PCR (quantitative real time polymerase chain reaction).
Results
Our study demonstrated significant upregulation of both Wnt3 and LEF1 in CLL (
P
< 0.0001). WNT3 and LEF1 were significantly decreased in CLL patients with ECOG performance 2 and 3 than those with 0 and 1 (
p
= 0.023 and 0.007, respectively). CLL patients with 17p deletion express significantly low LEF1 (
p
= 0.033). Low levels of WNT3 and LEF1 expression indicated a shorter overall survival (
P
= 0.007, 0.005, respectively). The predictive power of WNT3 and LEF1 expression showed good discrimination of CLL patients from controls (AUC >0.9).
Conclusion
Upregulation of WNT3 and LEF1 could be used as helpful and specific markers to distinguish our CLL patients. Low WNT3 and LEF1 expression is associated with shortened survival in CLL patients. These results indicate that WNT3 and LEF1 represent an attractive therapeutic target for future therapies in Egyptian CLL patients.
Chronic lymphocytic leukemia (CLL), a hematologic malignancy, characterized by progressive accumulation of mature B lymphocytes. The role of Wnt signaling pathway has been reported in CLL biogenesis. ...Lymphoid enhancer-binding factor-1 (LEF1), a mediator of this canonical pathway has been identified in CLL.
To analyze Wnt signaling pathway members (WNT3) and its key mediator LEF1 expression levels in CLL patients and to assess their potential role as markers of CLL outcome.
An observational prospective study from February 2017 till February 2018.
It was carried out in the Hematology unit at Oncology Center Mansoura University (OCMU).
This study was carried out on 35 newly diagnosed CLL patients in comparison with 15 adult controls, they were M/F 14/16 (47/53%), median age 63.
The patients were subjected to history taking, physical examination and laboratory investigations of CLL. Wnt3 gene and LEF1 expression levels in peripheral blood of untreated CLL mononuclear cells and normal healthy controls were determined by RT-PCR.
Our study demonstrated significant upregulation of both Wnt3 and LEF1 in CLL PBMNC in comparison to healthy controls (P<0.0001).
WNT3 and LEF1 were significantly decreased in CLL patients with ECOG 2&3 P=0.023 and 0.007, respectively. Untreated CLL patients harboring 17p deletion expressed significantly low LEF1 (P=0.033). A significant positive association was observed between WNT3 and LEF1 levels (Spearman r=0.74, P<0.0001). Low WNT3 and LEF1 mRNA expression levels indicated a shorter OS. The median survival in Low WNT3 and LEF1 and high WNT3 and LEF1 patients were 7 (P=0.007) and 11 (P=0.005) months, respectively. Moreover, ROC curve of WNT3 and LEF1 expression levels was conducted for discrimination between CLL and healthy controls with good AUC 0.95 and 0.96, respectively.
WNT3 and its key mediator LEF1 were shown to be overexpressed and activated in CLL cells in comparison to healthy persons. Raising the interest that antagonizing Wnt signaling in CLL may represent an effective treatment potential. Interestingly, low expression of both WNT3 and LEF1 were associated with shortened survival in CLL patients which trigger more studies on a larger patient cohort.
Hodgkin lymphoma (HL) is a heterogeneous group of neoplasms that makes up 10% of lymphomas. HL cases treated with radiotherapy have an increased risk of developing papillary thyroid carcinoma (PTC). ...However, the concomitant de novo PTC and HL are quite rare. Moreover, immune cytopenia is reported with lymphoproliferative diseases. Yet they are rarely described in HL patients.
This report highlights two rare concomitant associations (PTC and ITP) in an HL case and the case management.
Case study.
Hematology Unit, Oncology Center, Mansoura University.
A young male patient was referred from the surgical department due to progressive severe thrombocytopenia after total thyroidectomy. The pathology revealed PTC (follicular variant) with no nodal involvement, which was confirmed by pathology and thyroid scan. Several months later, he was diagnosed with HL.
The patient underwent all testing, including immune work-up, and viral markers were negative. His coagulation profile and BM examination were normal (except for an increase in mature and immature megakaryocytes). He was diagnosed with idiopathic thrombocytopenia, and steroid therapy was commenced. However, there was no improvement. Two months later, several cervical LNs were noted. Lymph node biopsy revealed Hodgkin lymphoma (mixed cellularity). BM trephine biopsy showed that all hematopoietic series were normal with no infiltration of abnormal cells. Meanwhile, his platelet count was less than 10,000/mcl and not responding to other conventional treatment over these 2 months.
The patient started eltrombopag 50 mg for 2 weeks and then was treated with ABVD protocol. Eltrombopag helped to raise and maintain a safe platelet count, and he was able to receive his chemotherapy cycles efficiently.
After 2 cycles of ABVD, his platelet count was normalized and eltrombopag was decreased gradually and then stopped. PET CT after he finished chemotherapy courses revealed a complete remission response. He is now finishing his consolidative cycles of AVD.
The synchronous occurrence of PTC, ITP, and HL is an extremely rare condition that posed a significant treatment dilemma. Using thrombopoietin receptor agonists may help in this setting.