[Influence of dasatinib treatment on body height in children with acute myeloid leukemia].
Zhongguo Dang Dai Er Ke Za Zhi. 2020 Jan;22(1):47-52
Authors: Zheng FY, Lu AD, Zhang LP, Zuo YX, Jia YP, Wu J
OBJECTIVE: To study the influence of dasatinib treatment on body height in children with acute myeloid leukemia (AML).
METHODS: A retrospective analysis was performed for the clinical data of 86 AML children aged <17 years. According to the treatment regimen, these children were divided into a conventional chemotherapy group and a dasatinib chemotherapy group. The 57 children in the conventional chemotherapy group were given conventional chemotherapy drugs without tyrosine kinase inhibitor, and the 29 children in the dasatinib chemotherapy group were given conventional chemotherapy drugs and dasatinib. The two groups were compared in terms of height standard deviation score (HtSDS) at the beginning of treatment and after treatment, as well as the change in HtSDS after 1 and 2 years of treatment.
RESULTS: There was no significant difference in HtSDS between the conventional and dasatinib chemotherapy groups before treatment. Within the first two years of treatment, the dasatinib chemotherapy group had a similar change trend of HtSDS as the conventional chemotherapy group. Four children in the dasatinib chemotherapy group reached the final adult height during follow-up, which was significantly lower than the target height (P=0.044). In the conventional chemotherapy group, there was no significant difference between final adult height and target height. In the dasatinib chemotherapy group, the children in adolescence had a significant change in HtSDS after treatment (P=0.032).
CONCLUSIONS: Dasatinib treatment may affect the final height of children with AML, and the use of dasatinib after the beginning of adolescence may lead to growth disorder, but dasatinib treatment has little effect on body height in the short-term treatment.
PMID: 31948524 [PubMed - indexed for MEDLINE]
Mucormycosis in a patient with acute myeloblastic leukemia following liver transplantation for Wilson's disease.
Ann Agric Environ Med. 2019 Dec 19;26(4):665-668
Authors: Łanocha AA, Guzicka-Kazimierczak R, Zdziarska B, Wawrzynowicz-Syczewska M
A case is presented of mucormycosis in a patient with acute myeloblastic leukemia following liver transplantation for Wilson's disease. A 58-year-old female was admitted to the Department of Haematology with deterioration of her general condition, loss of appetite, tiredness and difficulty with mental contact for a few days. Blood and urine cultures for bacteria and fungus, galactomannan antigen were negative. Whole body computed tomography demonstrated bilateral hilar lymphadenopathy with necrotic lesions: splenomegaly with a hypodensive lesion 13 × 20 × 19 mm and lower pulmonary infiltrates suggested fungal etiology. Magnetic resonance imaging of the brain showed thickened meninges. Finally, mucormycosis was diagnosed. Treatment with amphotericin B lipid complex was started, resulting in an partial improvement of the general condition and decreased level of inflammatory markers. However, the patient's condition continued to deteriorate, with sepsis etiology Escherichia coli, and despite the intensive managements she eventually died.
PMID: 31885243 [PubMed - indexed for MEDLINE]
LncRNA KCNQ1OT1 contributes to the progression and chemoresistance in acute myeloid leukemia by modulating Tspan3 through suppressing miR-193a-3p.
Life Sci. 2020 Jan 15;241:117161
Authors: Sun H, Sun Y, Chen Q, Xu Z
AIMS: Acute myeloid leukemia (AML) is an aggressive cancer that invariably produces drug resistance after treatment. The aim is to explore the role of lncRNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1) and associated novel mechanisms in the progression and chemoresistance of AML.
MAIN METHODS: The expression of KCNQ1OT1, miR-193a-3p, and Tspan3 was measured by qRT-PCR. The values of IC50 for adriamycin (ADR) and the ability of proliferation were analyzed by CCK-8 assay. Cell migration and invasion were assessed by transwell assay. Cell apoptosis was monitored by flow cytometry assay. The expression of Tspan3, MRP1, P-gp and LRP at the protein level was quantified by western blot. The relationship between miR-193a-3p and KCNQ1OT1 or Tspan3 was predicted by bioinformatics tool Diana and verified by dual-luciferase reporter assay, RIP assay or RNA pull-down assay.
KEY FINDINGS: KCNQ1OT1 and Tspan3 were up-regulated, while miR-193a-3p was down-regulated in ADR resistant AML samples and cells. KCNQ1OT1 knockdown reduced ADR resistance, inhibited proliferation, migration and invasion but promoted apoptosis of ADR resistant AML cells, miR-193a-3p inhibition reversed these effects. MiR-193a-3p was a target of KCNQ1OT1 and combined with Tspan3 3' untranslated region (3' UTR). Enrichment of miR-193a-3p decreased ADR resistance, inhibited proliferation, migration and invasion and stimulated apoptosis in ADR resistant AML cells, but Tspan3 overexpression overturned these impacts.
SIGNIFICANCE: KCNQ1OT1 aggravates AML progression and chemoresistance to ADR by inducing Tspan3 expression via adsorbing miR-193a-3p in ADR resistant AML cells, providing a theoretical basis for the treatment of AML with chemoresistance.
PMID: 31837329 [PubMed - indexed for MEDLINE]
Treatment of primary plasma cell leukemia with high doses of cyclophosphamide, bortezomib, and dexamethasone followed by double autologous HSCT.
Ann Hematol. 2020 Jan;99(1):207-209
Authors: Pagano L, Maraglino AME, Fianchi L, Criscuolo M, Rossi E, Za T, Chiusolo P, Bonanni M, Dragonetti G, Bacigalupo A, Sica S, De Stefano V
PMID: 31832752 [PubMed - indexed for MEDLINE]
The pro-apoptotic effect of a Terpene-rich Annona cherimola leaf extract on leukemic cell lines.
BMC Complement Altern Med. 2019 Dec 12;19(1):365
Authors: Ammoury C, Younes M, El Khoury M, Hodroj MH, Haykal T, Nasr P, Sily M, Taleb RI, Sarkis R, Khalife R, Rizk S
BACKGROUND: The edible fruit Annona cherimola has previously shown many nutritional and medicinal properties. The current study evaluates the anti-cancer and anti-proliferative properties of Annona cherimola ethanolic leaf extract (AELE) on Acute Myeloid Leukemia (AML) cell lines cultured in vitro (Monomac-1 and KG-1).
METHODS: The anti-proliferative effect of A. cherimola ethanolic leaf extract was evaluated via cell viability assay. Its pro-apoptotic effect was assessed through Cell Death ELISA and dual Annexin V/PI staining. To further investigate the molecular mechanism by which the extract promoted apoptosis and inhibited the proliferation of the AML cells used, apoptotic protein expression was determined through western blots. Extract composition was elucidated by Gas Chromatography-Mass Spectrometry (GC-MS).
RESULTS: Our results showed that the treatment with A. cherimola ethanolic leaf extract exhibited an inhibitory effect on the proliferation of both cancer cell lines used in a dose- and time-dependent manner, with no toxic effects on normal mononuclear cells (MNCs) isolated from human bone marrow. This effect was mediated by DNA fragmentation and apoptosis, as revealed by Cell Death ELISA and dual Annexin V/PI staining. Western blot analysis revealed a Bax/Bcl2 dependent mechanism of apoptosis, as well as PARP cleavage, confirming the apoptotic results observed previously. These effects may be attributed to the presence of terpenes which constitute a large component of the leafy extract, as revealed via GC-MS.
CONCLUSION: All the data presented in our study show that the terpene-rich A. cherimola ethanolic leaf extract exhibits an anti-proliferative and pro-apoptotic effect on the AML cell lines used.
PMID: 31830975 [PubMed - indexed for MEDLINE]
Recent advances in the understanding and therapeutic management of mastocytosis.
Authors: Rossignol J, Polivka L, Maouche-Chrétien L, Frenzel L, Dubreuil P, Hermine O
Mastocytosis is a rare disease due to the abnormal accumulation of mast cells in various tissues. Its clinical presentation is heterogeneous depending on mast cell infiltration and mediators release. In some cases, it is associated with hematological malignancies. Prognosis varies from very good with a life expectancy similar to the general population in indolent forms of the disease to a survival time of just a few months in mast cell leukemia. Although in most cases a somatic KIT D816V mutation is found in tumor mast cells, the physiopathology of the disease is not yet fully understood. Additional germline and somatic mutations may explain this heterogeneity. Treatments aim at blocking effect of mast cell mediators, reducing mast cell activation and tumor burden. New drugs mainly directed against the tyrosine kinase activity of KIT have dramatically changed the quality of life and prognosis of mast cell diseases. Present and future therapeutic strategies are discussed in this review.
PMID: 31824655 [PubMed - indexed for MEDLINE]
MEF2D-rearranged acute lymphoblastic leukemia resembles Burkitt lymphoma/leukemia.
Ann Hematol. 2020 Jan;99(1):185-188
Authors: Sun J, Yu W, Zhang X
PMID: 31781846 [PubMed - indexed for MEDLINE]
Magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography/computed tomography findings in neurolymphomatosis: an uncommon presentation of diffuse large B cell lymphoma.
Ann Hematol. 2020 Jan;99(1):203-205
Authors: Switlyk MD, Skeie AT, Lund-Iversen M, Østenstad B
PMID: 31768676 [PubMed - indexed for MEDLINE]
Systemic mastocytosis associated with acute myeloid leukemia.
Ann Hematol. 2020 Jan;99(1):195-196
Authors: Nogueira FL, Martins NNN, Cardoso PSR, Murao M, de Melo FHC, Glória ABF, Fagundes EM
PMID: 31768674 [PubMed - indexed for MEDLINE]
A review of bioanalytical methods for chronic lymphocytic leukemia drugs and metabolites in biological matrices.
Biomed Chromatogr. 2020 Jan;34(1):e4742
Authors: P S S, Trivedi RK, Srinivas NR, Mullangi R
Quantitation of drugs used for the treatment of chronic lymphocytic leukemia in various biological matrices during both pre-clinical and clinical developments is very important, often in routine therapeutic drug monitoring. The first developed methods for quantitation were traditionally done on LC in combination with either UV or fluorescence detection. However, the emergence of LC with mass spectrometry in tandem in early 1990s has revolutionized the quantitation as it has provided better sensitivity and selectivity within a shorter run time; therefore it has become the choice of method for the analysis of various drugs. In this article, an overview of various bioanalytical methods (HPLC or LC-MS/MS) for the quantification of drugs for the treatment of chronic lymphocytic leukemia, along with applicability of these methods, is given.
PMID: 31749152 [PubMed - indexed for MEDLINE]
Peripheral T cell lymphoma after chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): a case report.
BMC Neurol. 2019 Nov 04;19(1):266
Authors: Liu XH, Jin F, Zhang M, Liu MX, Wang T, Pan BJ, Zhang L
BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological characteristics. The pathophysiology of CLIPPERS still remains unclear. Because a few cases about lymphoma mimicking the manifestations of CLIPPERS were reported and the prognosis of lymphoma is much worse, early identification of lymphoma is very important.
CASE PRESENTATION: A 31-year-old woman was admitted with 3 months' history of diplopia, dizziness, gait ataxia, and right facial numbness. The diagnosis of CLIPPERS was established based on the finding of punctate enhancing lesions in the cerebellum, thalamus, pons, medulla, and midbrain region in magnetic resonance imaging (MRI), together with the favorable clinical and radiological responses to corticosteroids. However, she was diagnosed as peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) by the pulmonary nodular and the skin biopsy almost 10 years later, and she got complete remission within 1 year after chemotherapy.
CONCLUSION: We report the first case of CLIPPERS developing PTCL-NOS. This case proposes that when brain biopsy was difficult to achieve, biopsies in extra-cerebral lesions under the assisting examination of positron emission tomography-computed tomography (PET-CT) can be helpful in further identification.
PMID: 31684908 [PubMed - indexed for MEDLINE]
Parenchymal central nervous system involvement in aggressive B-cell lymphoma: retrospective analysis of clinical and MRI features in a Chinese population.
BMC Neurol. 2019 Nov 04;19(1):268
Authors: Wu Y, Wang Y, Sun X, Bai X, Qian J, Zhu H, Cui Q, Xing R, Chen Y, Liu Q, Guo J, Ji N, Sun S, Liu Y
BACKGROUND: Secondary central nervous system lymphoma (SCNSL) is defined as secondary central nervous system (CNS) involvement in patients with systemic lymphoma. It is considered a profoundly adverse complication with inferior clinical outcome. Parenchymal involvement in the CNS in aggressive B-cell lymphoma is not frequently seen and remains a diagnostic dilemma.
METHODS: In our study, we retrospectively analyzed the clinical and magnetic resonance imaging (MRI) features of 26 parenchymal SCNSL patients. In addition, we compared MRI features of SCNSL and primary CNS lymphoma (PCNSL) patients after 1:1 propensity score matching. Also we presented two SCNSL cases with atypical MRI appearance.
RESULTS: Among SCNSL patients, the median CNS relapse time was 3 months, and multiple lesions were found in 76.9% of the cases. In PCNSL, this percentage was 42.3% (p = 0.011). None of the SCNSL patients and 23.1% of the PCNSL patients had solitary infratentorial lesions (p = 0.003).
CONCLUSIONS: The majority of parenchymal involvement occurred within the first year of systemic lymphoma, in which mostly cases presenting with multiple and supratentorial locations, unlike what was found in PCNSL.
PMID: 31684888 [PubMed - indexed for MEDLINE]
Tumoral Mimics of Subdural Hematomas: Case Report and Review of Diagnostic and Management Strategies in Primary B-Cell Lymphoma of the Subdural Space.
World Neurosurg. 2020 Jan;133:49-54
Authors: Neeley OJ, Al-Hreish KM, Aoun SG, El Ahmadieh TY, Plitt A, Vance AZ, Jaso JM, Hatanpaa KJ, White JA
BACKGROUND: Subdural lymphomas are a rare subtype of primary central nervous system lymphomas that can radiographically mimic epidural blood and pose a diagnostic challenge. They can complicate treatment if not preemptively identified.
METHODS: We present a case report of a subdural lymphoma that mimicked a compressive subdural hematoma, and we review the PubMed database for similar cases.
RESULTS: A 77-year-old woman presented with a transient left facial droop and what appeared to be a subdural hematoma on computed tomography scan. The patient underwent surgery, during which grossly abnormal solid epicortical adherent tissue was noted instead of the expected appearance of a subdural hematoma. An intraoperative biopsy was suggestive of lymphoma, and the surgery was converted to a craniectomy. Pathology confirmed the diagnosis of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The patient underwent radiotherapy with no complications or recurrence. Magnetic resonance imaging demonstrated complete resolution of the mass at 3 months after treatment, at which time the patient underwent a synthetic cranioplasty. Seven case reports of primary dural lymphomas mimicking subdural blood were found, with variable pathologic subclassifications.
CONCLUSIONS: Although rare, a primary dural lymphoma can be mistaken for a subdural hematoma on computed tomography scan. The most common subtype is low-grade extranodal marginal zone lymphomas. It is important to keep these diseases in the differential diagnosis, especially when there is incongruence between imaging and the clinical picture, as earlier detection correlates to a stronger therapeutic response.
PMID: 31562973 [PubMed - indexed for MEDLINE]
Expression of blood hepatocyte-derived microRNA-122 in canine multicentric lymphoma with hepatic involvement.
Vet Res Commun. 2019 Nov;43(4):231-238
Authors: Ramadan ES, Kubesy AA, Baraka TA, Torad FA, Salem SI, Salem NY
This study was performed to evaluate the hepatocyte-derived microRNA (miR)-122 as novel diagnostic biomarker in canine lymphoma. Fifteen dogs were enrolled in this study. Dogs presented at Small Animal Teaching Hospital, Faculty of Veterinary Medicine, Cairo University. Dogs were divided into 8 clinically healthy dogs act as control and 7 clinically ill dogs. All dogs were subjected to clinical, ultrasonographic, hemato-biochemical and ultrasound-guided fine-needle biopsy for cytological and histopathological investigations. On the basis of these results, 7 dogs were found to be suffering from multicentric lymphoma involving liver. Serum hepatocyte-derived miRA-122 was determined by real-time quantitative polymerase chain reaction in all dogs. Multicentric lymphoma involving liver manifested by inappetance for several days, depression and peripheral lymphadenopathy. Hematological examination showed significant lymphocytosis. Serum biochemical analysis revealed significant increase in ALT, AST, ALP compared to control dogs. Ultrasonography revealed hypoechoic lymphoid aggregation at area of "porta hepatis" and circumscribed hypoechoic nodule interrupt liver parenchyma. Cytology revealed infiltration of liver tissue by lymphoblast cells and histopathology revealed diffuse infiltration of hepatic sinusoids and portal area by uniform population of small lymphocytes. Serum miRNA-122 analysis showed a significant increase represented as 9.00 fold in canine multicentric lymphoma involving liver. Serum hepatocyte-derived miRNA-122 is of diagnostic value, non invasive, stable and easily measurable blood biomarker for the detection of hepatocellular injury in dogs with multicentric lymphoma involving liver.
PMID: 31473888 [PubMed - indexed for MEDLINE]
Continuous intrathecal injection therapy of methotrexate is a therapeutic option in primary CNS lymphoma.
J Clin Neurosci. 2019 Nov;69:26-30
Authors: Otani R, Yamada R, Kushihara Y, Inazuka M, Shinoura N
Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin's lymphoma, and its prognosis is still very poor despite the conventional therapy of high-dose methotrexate (HD-MTX) followed by whole-brain radiation therapy (WBRT). The purpose of the present study was to evaluate the survival benefit of continuous intrathecal injection therapy of methotrexate (CIT-MTX) combined with the conventional therapy. A total of 26 PCNSL patients treated with CIT-MTX were analyzed. Ten mg of methotrexate were continuously injected into the lateral ventricle via a subcutaneous port over 5 days biweekly for 5 cycles. CIT-MTX was performed with WBRT in addition to HD-MTX in 15 cases, and 11 cases with high risk for HD-MTX were treated with CIT-MTX and WBRT. The response rate of all patients was 92.3%, and median progression-free survival and median overall survival (mOS) were 59.4 months and 93.8 months, respectively. Median OS of patients treated with CIT-MTX in addition to HD-MTX and WBRT was longer than the previously reported mOS with HD-MTX and WBRT (95 vs 33 months). In cases that could not tolerate HD-MTX, mOS of patients treated with CIT-MTX and WBRT was longer than the previously reported mOS with WBRT alone (36.7 vs 18 months). There was no difference in OS between patients with cerebrospinal fluid dissemination and patients without (p = 0.83). Better prognosis in patients treated with CIT-MTX may be derived from stable concentration of methotrexate in the cerebrospinal fluid. CIT-MTX was an effective additional therapeutic option for PCNSL.
PMID: 31466902 [PubMed - indexed for MEDLINE]
Pretreatment intratumoral susceptibility signals correlate with response to high-dose methotrexate and progression-free survival in primary central nervous system lymphoma.
J Clin Neurosci. 2019 Nov;69:43-50
Authors: Deguchi S, Nakashima K, Muramatsu K, Mitsuya K, Oishi T, Shirata K, Hayashi N, Sugino T, Endo M, Nakasu Y
We aimed to estimate the frequency of intratumoral susceptibility signals (ITSS) in susceptibility-weighted imaging (SWI) in consecutive patients with primary central nervous system lymphoma (PCNSL), and to determine if pretreatment heterogeneity of PCNSL is predictive of response to chemotherapy by using ITSS on SWI. We retrospectively examined 29 immunocompetent patients with PCNSL who underwent SWI-MRI before treatment. A univariate analysis was conducted with Fisher's exact test. Progression free survival (PFS) was calculated by the Kaplan-Meier method and compared by the log rank test. The patients, including 16 males, were initially treated at a median age of 69 years. All tissue types were diffuse large B-cell lymphoma. Nineteen patients (66%) presented lesions with ITSS. Sixteen patients (55%) received initial treatment with R-MTX (rituximab plus high-dose methotrexate). Seven out of nine patients with ITSS exhibited a poor response, whereas all seven without ITSS exhibited a good response to R-MTX. Regarding the absence of ITSS, the sensitivity, specificity, and diagnostic accuracy for a good response to R-MTX were 0.78, 1.00, and 0.88, respectively. Patients without ITSS showed significantly longer PFS compared to patients with ITSS (median PFS: 28.9 vs 2.1 months, P < 0.01). In conclusion, ITSS in PCNSL patients were more common than previously reported. We have to be careful to use ITSS for differentiating PCNSL and glioblastoma. Presence of ITSS correlated significantly with therapeutic response to R-MTX. ITSS may be a new marker for the response to chemotherapy in patients with PCNSL. A prospective multi-institutional analysis is needed.
PMID: 31427235 [PubMed - indexed for MEDLINE]
Oxidative phosphorylation inhibition induces anticancerous changes in therapy-resistant-acute myeloid leukemia patient cells.
Mol Carcinog. 2019 11;58(11):2008-2016
Authors: Vitkevičienė A, Janulis V, Žučenka A, Borutinskaitė V, Kaupinis A, Valius M, Griškevičius L, Navakauskienė R
Treatment of acute myeloid leukemia (AML) is still a challenge because of common relapses or resistance to treatment. Therefore, the development of new therapeutic approaches is necessary. Various studies have shown that certain cancers, including some chemoresistant AML subsets, have upregulated oxidative phosphorylation. In this study, we aimed to assess treatment-resistant AML patients' cell modulation using oxidative phosphorylation inhibitors metformin and atovaquone alone and in various combinations with cytosine analog cytarabine and apoptosis inducer venetoclax. Metabolic activity analysis using Agilent Seahorse XF Extracellular Flux Analyzer revealed that peripheral blood mononuclear cells' metabolic state was different among treatment-resistant AML patients. We demonstrated that metformin decreased therapy-resistant-AML cell oxidative phosphorylation ex vivo, cotreatment with cytarabine and venetoclax slightly increased the effect. However, treatment with atovaquone did not have a marked effect in our experiment. Cell treatment had a slight effect on cell proliferation inhibition; combination of metformin, cytarabine, and venetoclax had the strongest effect. Moreover, a slightly higher effect on cell proliferation and cell cycle regulation was demonstrated in the cells with higher initial oxidative phosphorylation rate as demonstrated by gene expression analysis using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Proteomic analysis by liquid chromatography-mass spectrometry demonstrated that chemoresistant AML cell treatment with metformin modulated metabolic pathways, while metformin combination with cytarabine and venetoclax boosted the effect. We suggest that oxidative phosphorylation inhibition is effective but not sufficient for chemoresistant AML treatment. Indeed, it causes anticancerous changes that might have an important additive role in combinatory treatment.
PMID: 31385375 [PubMed - indexed for MEDLINE]
Keeping Our Finger on the Pulse: Reaffirming the Role of Radiation Therapy in the Curative Management of Early Stage Follicular Lymphoma.
Int J Radiat Oncol Biol Phys. 2019 11 01;105(3):459-465
Authors: Campbell BA, Plastaras JP, Savage KJ
PMID: 31254657 [PubMed - indexed for MEDLINE]
Limited Tissue Samples: Hematopoietic Lesions - Three Case Examples of Judicious Use of Limited Material.
Acta Cytol. 2020;64(1-2):71-80
Authors: Chadburn A, Chen YH, Nayar R, Young A, Sumpter I, Lee C, Gill M, Gao J
In the era of smaller and smaller biopsies submitted to pathology departments for diagnosis and the advent of personalized medicine, it has become imperative to efficiently and effectively use patient material to reach individualized, actionable diagnoses. The use of fine needle aspirates and core biopsies as acceptable methods for obtaining sufficient material for hematopoietic neoplasms under nonemergent conditions is debatable. There are, however, scenarios where only limited material is obtainable due to anatomic site, size of the lesion or condition of the patient. In these types of settings, thoughtful approaches and unconventional means are often necessary to reach a diagnosis. In this article, we describe three such scenarios and the unique tactics taken in each to obtain a personalized actionable diagnosis.
PMID: 31063996 [PubMed - indexed for MEDLINE]
Flower cells of tropical descent: a challenging case of adult T-cell leukemia/lymphoma.
Tumori. 2019 Dec;105(6):NP38-NP42
Authors: Martino G, Zanelli M, Marra A, Quintini M, Zizzo M, Ascani S, Martelli MP, Falini B
BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease associated with human T-lymphotropic virus type 1 infection, with a very high prevalence in tropical areas but exceptionally rare in Europe and Western countries.
CASE PRESENTATION: We describe a challenging case of ATLL in a young male patient with Brazilian origin and adopted as a child by an Italian family, presenting to our clinic with atypical T-lymphocytosis and life-threatening lung infections.
CONCLUSIONS: Diagnosis of ATLL outside of endemic areas can be difficult, requiring a high index of clinical suspicion with careful evaluation of the patient's clinical history. Prognosis is affected by disease stage at presentation and degree of immunosuppression. Few effective treatments are available, although new molecular insights have highlighted the role of host immune response and immune checkpoint blockade inhibitors, given the overexpression of PD-L1 on lymphoma cells and on microenvironment cells.
PMID: 31041884 [PubMed - indexed for MEDLINE]
The effects of erythropoiesis-stimulating agents on the management of chemotherapy-induced anemia and tumor growth in diffuse large B-cell lymphoma patients.
Int J Cancer. 2019 11 01;145(9):2459-2467
Authors: Park LC, Song YJ, Kim DJ, Kim MJ, Jo JC, Lee WS, Shin HJ, Oh SY, Do YR, Jeong JY, Lee HS, Consortium for Improving Survival of Lymphoma (CISL)
Erythropoiesis-stimulating agents (ESAs), such as erythropoietin (EPO) and darbepoetin, may alleviate anemia in diffuse large B-cell lymphoma (DLBCL) patients. However, many cancer cells express EPO receptors (EPOR), through which exogenously administered ESAs potentially promote cancer cell growth. We conducted preclinical/phase II studies to investigate the safety and efficacy of ESAs for managing chemotherapy-related anemia in DLBCL patients. We examined EPOR expression in germinal center B-cell (GCB)- and activated B-cell (ABC)-DLBCL cell lines, and investigated the effects of ESAs on cell proliferation, and rituximab-mediated complement-dependent cytotoxicity (CDC). The clinical study enrolled 50 histologically confirmed DLBCL patients receiving rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP) who had hemoglobin levels <10.0 g/dl after a maximum of three R-CHOP cycles and received ≥4 doses of fixed-dose darbepoetin (360 μg) once every 3 weeks. EPOR mRNA was detected in all GCB-DLBCL cell lines, but little/none was detected in ABC-DLBCL cell lines. GCB-DLBCL and ABC-DLBCL cell proliferation was unaffected by EPO or darbepoetin. Rituximab-mediated CDC of DLBCL cell lines with/without EPOR expression was not affected adversely by EPO. In the clinical study, baseline mean hemoglobin was 9.19 g/dl; the overall mean change in hemoglobin was 1.59 ± 1.3 g/dl (16 weeks). Forty-eight percent of enrolled patients achieved a hematopoietic response. Our study shows that ESAs do not affect the growth of DLBCL cells or rituximab-mediated CDC under the experimental conditions that we used, and the appropriate use of ESAs may be effective and safe for DLBCL patients with anemia after R-CHOP.
PMID: 30973963 [PubMed - indexed for MEDLINE]
Clinical characteristics and prognosis associated with multiple primary malignant tumors in non-Hodgkin lymphoma patients.
Tumori. 2019 Dec;105(6):474-482
Authors: Jiang Y, Miao Z, Wang J, Chen J, Lv Y, Xing D, Wang X, Wang Y, Cao Z, Zhao Z
OBJECTIVE: Patients with non-Hodgkin lymphoma (NHL) occasionally present with multiple primary malignant tumors (MPMTs). This study aimed to determine the clinical characteristics, survival, and risk factors of these patients.
METHODS: The median follow-up of 92 patients was 13.5 months (range 0.3-72). Overall, 21 patients had synchronous MPMTs and 71 had metachronous MPMTs. We classified patients in the latter group into metachronous first group (n=27) and metachronous second group (n=44).
RESULTS: Diffuse large B-cell lymphoma was the most frequent histologic lymphoma type. The digestive system was the commonest site affected by the solid cancer. The 1- and 2-year survival rates were 86.5% and 70.5%, respectively. The overall survival (OS) rates were 67.9% and 36.2% at 2 and 3 years, respectively, in the metachronous first group; 73.8% and 73.8%, respectively, in the metachronous second group; and 68.1% and 56.7%, respectively, in the synchronous tumor group. There was no difference in the survival rate among the 3 groups before 2 years, but after 2 years, a shorter OS rate was observed in the metachronous first group than in the metachronous second group and synchronous tumor group. For all patients, age >60 years, male sex, and ⩾3 involved nodal sites were considered independent prognostic factors associated with survival.
CONCLUSIONS: OS time was shorter in patients with NHL who developed a second tumor than in those who were diagnosed with solid cancer synchronously and second neoplasm after previous solid tumors. Long-term follow-up and effective treatment should be provided to these patients.
PMID: 30945608 [PubMed - indexed for MEDLINE]
Fulminant blast crisis with de novo 11q23 rearrangement in a Philadelphia-positive CML patient undergoing treatment with dasatinib.
Tumori. 2019 Dec;105(6):NP8-NP11
Authors: Janjetovic S, Asemissen AM, Dicker F, Binder M, Dierlamm J, Bokemeyer C, Schafhausen P
BACKGROUND: Progression of chronic myeloid leukemia (CML) is frequently accompanied by cytogenetic evolution, with an extra copy of the Philadelphia chromosome, trisomy 8 and 19, and isochromosome (17p) commonly detected. Translocations involving 11q23 chromosomal region have been rarely reported in CML. The few reported patients with blast crisis (BC) of CML carrying an 11q rearrangement have insufficient responses to tyrosine kinase inhibitors (TKIs) and possess a poor prognosis.
CASE REPORT: We report the case of a 30-year-old man with CML who had a fulminant myeloid BC 4 months after initiation of first-line therapy with the TKI dasatinib, despite showing an optimal response at the 3-month timepoint. Despite cytoreductive therapy with hydroxyurea and 3rd-generation TKI ponatinib, the patient died within 10 days after the diagnosis of BC. Cytogenetic analyses revealed additional genetic aberrations including trisomy 8 and t(9;11)(p21;q23) involving the mixed lineage leukemia (MLL) gene.
CONCLUSION: The presence of 11q23 rearrangements in the relapse clone in BC of CML most likely accounts for the adverse clinical outcome. Thus, in the case of rapid and unexpected BC, the presence of 11q rearrangements should be tested together with other additional chromosomal alterations, and immediate addition of chemotherapy to the TKIs should be evaluated.
PMID: 30935343 [PubMed - indexed for MEDLINE]