|Year : 2015 | Volume
| Issue : 7 | Page : 53-56
|Date of Web Publication||24-Nov-2015|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Haematology. J Can Res Ther 2015;11, Suppl S3:53-6
A study on the myeloperoxidase, nitrite and malondialdehyde levels in the PMNs isolated from the blood samples of patients with leukemia
thS. Mukherjee , A. Jain, S. Chadha
Amity University, Lucknow, Uttar Pradesh, India, E-mail: [email protected]
Background: Leukemias are a group of malignancies characterised by the invasion of the bone marrow by immature haematopoietic precursors and differentiation arrest at various maturation steps. Oxidative DNA damage induced by activated neutrophils is suggested to play a role in the observed association between chronic inflammation and cancer progression in leukemia. Hydrogen peroxide (H2O2) is an important factor in neutrophil-induced DNA strand breakage. Under normal circumstances, H2O2 is consumed by the neutrophilic enzyme myeloperoxidase (MPO) to form a highly microbicidal compound hypochlorous acid (hocl). Nitrite, the stable end product of nitric oxide (NO) produced by nitric oxide synthase is also present at the inflammatory sites and serves as an excellent MPO inhibitor. Since MPO inhibition increases the availability of H2O2 so the presence of nitrite can increase H2O2-mediated DNA strand breakage by neutrophils. Aim: The present study was undertaken to determine the levels of malondialdehyde (MDA), nitrite and MPO in the polymorphonuclear leukocytes (pmns) isolated from the blood of patients with leukemia. Materials and Methods: pmns were isolated from the blood following the procedure of Boyum et al., 1976. Nitrite content was measured in the lysed cell supernatant by using the Griess reagent. The MPO activity and MDA levels were measured spectrophotometrically. Results and Conclusion: The nitrite level in the pmns isolated from the blood of leukemic patients (580.43nmoles/5x 106 cells) was found to be greater than that of control samples (18.230.056 nmoles/5x 106 cells). In contrast the MPO activity in the pmns isolated from the patient's blood (0.125 U/5 x 106cells) was less than that of control (12.12U/5x106 cells). The MDA levels in the pmns isolated from the patient blood (7.2500.02 nmoles/5 x 106cells) were also found to be greater than those in the control (1.1230.08 nmoles/5 x 106cells). The results of the present study indicate that increased nitrite levels in leukemia may inhibit the MPO activity thereby increasing the availability of H2O2 and increasing oxidative damage. However, the results described in the present study constitute only a preliminary step in and far from any suggestive conclusion.
A pilot study to evaluate the malondialdehyde, nitrite and antioxidant levels in blood samples of patients with leukemia
thS. Chadha , P. Singh, S. Mukherjee
Amity University, Lucknow, Uttar Pradesh, India, E-mail: [email protected]
Background: Oxidative stress plays an important role in the pathogenesis of numerous degenerative or chronic diseases, including leukemia. The increased production and/or ineffective scavenging of oxidants play an important role in the progress of such disorders. Oxidants like reactive oxygen species (ROS), reactive nitrogen species (RNS), and sulphur-centered radicals etc. Alter the function of all major classes of biomolecules. The levels of oxidant molecules are controlled by various cellular enzymic and non-enzymic antioxidants. Nitric oxide (NO) which is synthesized by nitric oxide synthase is a polyfunctional signalling molecule controlling processes of vasodilatation, platelet aggregation, immunocytotoxicity and carcinogenesis. Analysis of nitrite and nitrate is used as an index of endogenous production of NO. Excess NO can damage DNA and can react with superoxide radical to form peroxynitrite, which is a highly damaging free radical. Aim: The aim of our study was to measure MDA (malondialdehyde), antioxidant enzymes (Superoxide dismutase and Catalase) and the nitrite in the polymorphonuclear leukocytes (pmns) isolated from blood sample of patients with leukemia. Materials and Methods: PMNs were isolated from the blood following the procedure of Boyum et al., 1976. Nitrite was measured in the lysed cell supernatant by using the Griess reagent. MDA levels and antioxidant enzymes Superoxide dismutase (SOD) and Catalase (CAT) activities were estimated spectrophotometrically. Results and Conclusion: The MDA levels in the pmns isolated from the patient blood (7.2500.02 nmoles/5 x 106cells) were greater than those in the control (1.1230.08 nmoles/ml). Furthermore, there was a decrease in the CAT and SOD activity in the pmns isolated from the blood of leukemia patients (CAT-0.7040.04 ΅moles of H2O2 utilized/min/ml and SOD-0.587 0.02 U/ml) as compared to the control (CAT-1.6840.056 ΅moles of H2O2 utilized/min/ml and SOD-1.24 0.032 U/ml). The nitrite levels in the pmns isolated from the blood of leukemia patients (580.43nmoles/5x 106 cells) was greater as compared to the control (18.230.056 nmoles/5x 106 cells). The results of the present study indicate increased oxidative stress and decreased antioxidant enzymes in the blood of leukemic patients which may contribute towards the progression of cancer. However, the results described in the present study constitute only a preliminary step in and far from any suggestive conclusion.
Plasmacytoma of body of sphenoid bone: A case report
Saroj Gupta Cancer Center and Research Institute, Kolkata,
West Bengal, India, E-mail: [email protected]
Background: Plasmacytoma (plasma cell neoplasm) presented as multiple myeloma, solitary plasmacytoma of bone (SBP) and extramedullary plasmacytoma (EMP). Types of plasmacytoma vary from one another in terms of clinical findings, treatment options and survival. Intracranial involvement of multiple myeloma is extremely rare event and rarely the first presentation of Multiple myeloma. Case Presentation: A case of 58 years old patient reported with an unusual clinical presentation and behavior of multiple myeloma where intracranial lesion arising from body of sphenoid. Initial biopsy proved plasmacytoma and later confirmed the case as multiple myeloma. Patient received palliative radiation and about to get chemotherapy. Conclusion: In any skull based lesion, multiple myeloma should be kept in the differential diagnosis.
Mesenteric panniculitis mimicking non-Hodgkin lymphoma:
A case report
thS. Gupta , P. Agarwal, S. Prakash, A. Srivastava
Sarojini Naidu Medical College, Agra, Uttar Pradesh, India, E-mail: [email protected]
Background: Mesenteric panniculitis is a rare, benign and chronic fibrosing inflammatory disease that affects the adipose tissue of the mesentery of the small intestine and colon. Sometimes mesenteric panniculitis may mimick Non Hodgkin lymphoma or may be associated with it. Patient usually present with lump and pain in abdomen. Materials and Methods: A 45 yrs male presented to us with complain of abdominal lump and off and on abdominal pain. On clinical and radio-pathological ground it was diagnosed a case of NHL. Patient received 6 cycles of CHOP regimens with good response. When surgical resection of the residual disease was done; the histo-pathology came out to be mesenteric panniculitis. Results: In view of persisting lesion and after convincing the patient, he underwent exploratory laprotomy with resection of mesenteric mass with ileal segment with anastomosis on 22/6/11 at surgery dept. The histo-pathology came out to be mesenteric panniculitis. Conclusion: This case was reported in view of the rarity of this entity and to give emphasis that biopsy is mandatory in such cases as sometimes mesenteric panniculitis may mimic NHL or may be associated with it.
Risen from the ashes - poor prognostic multiple myeloma patients presenting as paraplegia/paraparesis: Prospective observational analysis
thV. Kuriakose , A. Anand, K. P. Reshmi, P. S. Sabarinath
Government Medical College, Trivandrum, Kerala, India, E-mail: [email protected]
Background: Multiple myeloma is a plasma cell neoplasm, characterized by a heterogeneous myriad of presenting complaints, with about 20% of the patients presenting with features of paraparesis or paraplegia, due to spinal cord compression caused by vertebral collapse, compression or fracture. Aim: We prospectively analyzed the neurological response & tumour response of myeloma patients who presented with paraplegia/paraparesis, treated with 8 Gy/single # followed by bortezomib/lenalidomide/dexamethasone as induction chemotherapy and maintenance with lenalidomide and bisphosphonates. All patients were either ISS Stage 2 or 3. Materials and Methods: Newly diagnosed myeloma patients presenting with paraparesis/paraplegia (Grade 0-2) were enrolled (n = 30). The neurological parameters and the tumour characteristics were noted. All patients received 8 Gy/single #, BLD induction. Neurological response assessed weekly and tumour response at 6 months. At six months, if patient went in for VGPR/CR then maintainence lenalidomide. Bisphosphonates for two years. Results: Median time to any neurological response is 2.97 weeks and to best motor response was 4.87 weeks. 93.3% patients improved to Grade 4 or 5 power. Most of the patients achieved total pain relief. 86.6% patients had VGPR & CR combined with BLD regimen. When the duration of symptoms were less than 30 days at the time of presentation, the mean time to any response was 2.30 weeks, time to best motor grade was 4.17 weeks, compared to 5.14 and 7.14 weeks respectively, p = 0.01 and 0.019. At a median follow up of 21 months, 27 patients were alive and in remission. Conclusion: Early initiation of local radiation to the affected area and initiation of chemotherapy is of paramount importance to achieve maximal results with regards to improvement in neurological as well as disease status. Single RT of 8 Gy produces excellent neurological response and pain relief. 93.3% patients who presented in a bedridden state, went back to their the normal life We conclude our observation that bedridden myeloma patients had an excellent improvement in quality of life and disease control with a single 8 Gy XRT and BLD induction followed by lenalidomide maintenance, along with bisphosphonate therapy and henceforth should always be treated with a radical intent.
Febuxostat versus allopurinol for the prevention and treatment of hyperuricemia in chronic myelogenous leukemia with hyperleucocytosis
thR. Sharma , D. Abrol, G. D. Singh, S. L. Angurana
Government Medical College, Jammu, Jammu and Kashmir, India, E-mail: [email protected]
Background: Hyperuricemia is noticed in Chronic Myelogenous Leukemia (CML) patients with hyperleucocytosis either at presentation or after starting therapy with hydroxyurea/imatinib because of tumor cell kill. Aim: To know whether febuxostat is superior to allopurinol in terms of efficacy and toxicity as hypouricemic agent in CML patients with hyperleucocytosis. Materials and Methods: 82 patients of CML with TLC >50,000/cu.mm. Were randomized to receive either febuxostat (40 mg/day) or allopurinol (200-300 mg/day) beginning 2 days before starting hydroxyurea. Complete blood count, renal function tests, liver function tests, serum uric acid and LDH were done at baseline and 1 week after starting urate lowering therapy. Results: The entire cohort, with median age of 40 years (range 13-82 years) comprised of 45 males and 37 females. There were 41 patients in each arm. Mean TLC at presentation was 1,63,622/cu.mm. Mean Hb was 8.25g%. 8 (9.76%) patients had severe anemia Hb <6 g/dl at presentation. Mean LDH at presentation was 617 IU/ml. Baseline serum uric acid levels ranged from 2.6-11.5 mg/dl. 22 (26.83%) patients presented with serum creatinine >1.3 mg/dl from the very beginning. 31 (37.8%) patients presented with serum uric acid >7 mg/dl and 23 (28.05%) presented with serum uric acid >7.5 mg/dl. In our series, hyperuricemia was seen in 28% patients at presentation. The mean uric acid level at baseline (UA1) was 6.57 mg/dl and at 1 week post therapy (UA2) was 5.74 mg/dl. There was no difference between the two groups receiving febuxostat or allopurinol in terms of UA1 and UA2. Uric acid response rate (patients achieving serum uric acid levels <7.5 mg/dl after therapy) was seen in 38 patients in febuxostat arm and in 39 patients in allopurinol arm. This difference was statistically not significant. The mean reduction in uric acid levels by febuxostat was found to be 1.022 mg/dl (+/-0.69 SD) as compared to 0.6512 mg/dl (+/-0.61SD) with allopurinol and the difference was statistically significant (p = 0.012). 3 patients received packed rbcs transfusion for severe anemia (Hb <6 g/dl). SGOT and SGPT elevation was noticed in 4 patients in febuxostat and 5 patients in allopurinol arm. The liver enzyme elevation was less than thrice the upper limit of normal range (ULN). Conclusion: The study has shown that febuxostat (40 mg/day) might be superior to allopurinol in quantitative reduction of serum uric acid over the period of initial one week of therapy in CML patients with hyperleucocytosis.
Long term outcomes of primary lymphoma of the orbital adnexa: A 20-year single institution experience
thA. Rishi , S. Laskar, N. Khanna, M. Sengar, H. Menon, S. Epari,
J. S. Goda
Tata Memorial Centre, Mumbai, Maharashtra, India, E-mail: [email protected]
Background: Orbital lymphomas are rare and usually present as early stage disease. We evaluated the clinical outcomes and toxicities of radiation therapy (RT) in primary orbital lymphoma (POL), and studied the effect of various prognostic factors on clinical outcome. Materials and Methods: From 1990 to 2012, 81 consecutive patients with Stage IE/IIE (bilateral) primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma or diffuse large B-cell lymphoma (DLBL), treated at our institution were evaluated. Sixty-six patients had MALT and 16 had DLBL. Eleven patients (14%) had bilateral involvement. Radiotherapy was delivered by either 6 MV photons, electrons or 60Co γ-rays. Radiation doses ranged from 39.6-45 Gy. Local control (LC), relapse free survival (RFS), overall survival (OS) and acute and late side effects were evaluated. Results: The median follow-up was 44 months (IQR: 17-62 months). Sites involved were conjunctiva, lacrimal gland and soft-tissues in 25 (31%), 12 (15%) and 44 (54%) patients, respectively. Megavoltage beam (s) was used in 93% and electrons in 7% of cases. The dose delivered was 39.6 Gy in 25 (31%) and 45 Gy in 56 patients (69%). Complete response was seen in 76 (93.8%) patients. The 10-year overall survival (OS), relapse-free survival (RFS), and local control (LC) rates for the entire cohort were 95.1%, 92.5%, and 79.4%, respectively. The RFS was significantly better for MALT than DLBL (94% vs. 78.3%, respectively; p-0.004; HR-0.2; 95% CI-0.017-0.67). Superficial tumours (conjunctiva and lacrimal) had better outcome for MALT. Most common acute reaction was redness (93%) and watering (91%) of eyes. Radiation-related late sequelae were documented in all patients. Cataracts were observed in 21 patients. The cumulative incidence of cataract at 5 years was 54%. All patients underwent lens-replacement surgery and had good visual acuity thereafter. Other late sequelae were dry eyes-23 (28.4%) patients and retinal detachment in 1 patient. Conclusion: POL responds favorably to RT, with manageable late morbidities. Superficial tumours had better outcome as compared to deep tumours, MALT lymphomas of the orbit have a better outcome than DLBL.
Helical tomotherapy for myeloablative total marrow irradiation: A dosimetric study
thJ. S. Goda , R. Phurailatpam, K. Joshi, P. Tanawade, M. Mathankar, M. Mathews, S. Nojin Paul
Tata Memorial Centre, Navi Mumbai, Maharashtra, India, E-mail: [email protected]
Background: Total marrow irradiation can be used as an alternative to total body irradiation as a conditioning regimen prior to bone marrow transplant in hematologic malignancies, the purpose of this study is to evaluate the dosimetry of TMI using Helical Tomotherapy (HT). Materials and Methods: Whole body CT data sets of 8 patients (median age: range: 12-37years) with 5mm slice thickness were used for planning in HT (TPS version 4.2.3). The contouring of the target and organ at risks (OAR) were delineated (Oncentra Master Plan v 4.1). Two plans were generated using 5 cm and 2.5 cm field widths. The modulation factor and pitch was 3 and 0.3 respectively. Dose to PTV, oars, dose homogeneity, the dose conformation and treatment time were evaluated. The doses obtained were compared with the existing literature. The prescribed dose was 14.4 Gy in 8 fractions. Results: The mean PTV volume was 7341.28 cc (sd = 2353). The dose homogeneity index (HI) of PTV was 12.2 (sd = 4.73) for 2.5 cm_FW and 14.80 (sd = 2.33) for 5 cm_FW. The conformation number (CN) for 2.5 and 5 cm plans are 0.6387 (sd = 0.08) and 0.5915.5776 (sd = 0.09) respectively. The mean dose (Gy) to the oars were as follows for 2.5 cm_FW: eyes, lens, lungs, kidneys, heart, liver, and testes for are -4.5, 3, 6.5, 3.7, 6.18, 6.06, and 1.37. The mean dose (Gy) to the oars were as follows for 5 cm_FW: eyes, lens, lungs, kidneys, heart, liver, thyroid and testes for are 4.66, 3.4, 6.5, 3.7, 5.3, 6.22 and 1.44. The treatment time for 2.5 and 5 cm plans were as 42.9 minutes (sd = 5.11) and 21.4 minutes (sd = 2.73). Conclusion: 5 cm field width plans produces optimal dose volume parameters with deliverable treatment time. There was no difference in the HI, CN and dose to organs at risks (OAR) with either of the plans. However time taken for complete delivery of therapy was double with 2.5 cm plan as compared to 5 cm plan. Initial dosimetric analysis suggests that helical tomotherapy is a good modality for complex treatments like TMI.
Bilateral primary adrenal lymphoma: A rare case presentation
thK. Sarath Chandra Reddy , S. Kumar, R. Bilimagga, M. Aal
HCG Hospitals, Bengaluru, Karnataka, India, E-mail: [email protected]
Primary adrenal lymphoma (PAL) is very rare and only a few cases have been reported. We are presenting a case of 72-year-old man, with bilateral Primary Adrenal lymphoma presenting with adrenal insufficiency. Initially the patient presented with complaints of decreased urination, vomiting and abdominal pain in the upper abdomen. He underwent Trans-urethral resection of prostate (TURP) for suspicion of bladder outlet obstruction. Histopathological examination confirmed the diagnosis as Benign prostatic hyperplasia. An abdominal computerized tomography scan demonstrated bilateral adrenal lesions but did not demonstrate any other lesions. The patient was treated with Inj hydrocortisone and tablet sodamint resulting in total remission of symptoms and normalisation of serum sodium levels. To rule out the possibility of metastatic disease, a positron emission tomography (PET CT) scan was done showing lesions in the adrenal glands abutting the diaphragm and showing significant uptake. Endocrine evaluation showed decreased cortisol levels. Biopsy was performed and histopathological and immunohistochemistry showed features consistent with Diffuse large B-cell lymphoma. This case should remind clinicians that though it is a very rare scenario, Primary adrenal lymphoma may present as bilateral adrenal incidentaloma especially if the patient has adrenal insufficiency.
Multiple myeloma - presentation as diplopia
thA. S. Anand , P. S. Sabarinath, M. A. Anjana
Governmentt Medical College, Trivandrum, Kerala, India, E-mail: [email protected]
Background: Multiple myeloma, a plasma cell neoplasm usually presents with lumbar pain, paraesthesia, paraplegia, generalized weakness & renal failure. At the same time, very rare atypical presentations are noted. Case Report: We report a case of 59 yr old gentleman who presented with diplopia and facial paraesthesia. Clinical and ophthalmologic examination revealed 6th cranial nerve palsy and 5th cranial nerve involvement. Common benign & malignant causes were thought of and ruled out. A bone marrow was done, as all other initial work up were inconclusive. Surprisingly bone marrow aspiration revealed plasmacytosis > 30% and hence all other diagnostic & prognostic workup of myeloma was done. Diagnostic evaluation finally revealed multiple myeloma ISS Stage 3 with LDH elevated > ULN. He was started on chemotherapy with BLD (Bortezomib, Lenalidomide, Dexamethasone) in view of bad prognostic factors. After 3 months of treatment his lateral rectus palsy and facial paraesthesia completely resolved. Patient has now completed 6 months of treatment and achieved very good partial response. Discussion: As per literature atypical presentations of multiple myeloma include 6th cranial nerve palsy with or without other cranial nerve involvement, lung parenchymal involvement, ovarian involvement, amylodosis tongue. Mechanism of 6 th cranial nerve palsy include hematologic effect, compression effects or direct infiltration of the nerve itself. Conclusion: Atypical presentation of any malignancy may lead to delay in diagnosis and treatment. Henceforth knowledge of these types of rare presentations will definitely be an eye opener for treating physician for the benefit of patient care.
Supercilliary madarosis in an Indian male with chronic myelogenous leukemia treated with dasatinib
thS. Gupta , M. L. B. Bhatt, S. kumar, K. Pranay, M. Suhel, A. R. Kulshrestha, C. Awasthi, A. Batra
King Georges Medical University, Lucknow, Uttar Pradesh, India, E-mail: [email protected]
Background: Dasatinib, a second-generation multi-target tyrosine kinase inhibitor (TKI) is active against many imatinib-resistant BCR-ABL mutant forms, Src, and c-Kit tyrosine kinases. While skin hypopigmentation is a well recognized adverse effect of first generation TKIs; it has rarely been reported with dasatinib. We report a rare case of diffuse cutaneous hypopigmentation & bilateral supercilliary madarosis induced by dasatinib. Aim: To Present a rare case of diffuse cutaneous hypopigmentation & Supercilliary madarosis in an Indian male with Chronic Myelogenous Leukemia Treated with Dasatinib. Materials and Methods: A 51 yr old male patient, diagnosed with CML was referred to our department. In May 2005, he was started on tablet imatinib mesylate 400 mg OD. Quantitative bcr abl translocation assay (91%) & FISH for bcr-abl was also done in 2005 t(9;22). The transcript ratio on Quantitative bcr abl translocation assay ranged between 0-1% between September 2005 and November 2012. In April 2011, the patient visited a psychiatrist with complaints of anxiety, anger, desire to hurt and self harm. The patient was initiated on sodium valproate 750 mg OD, clonazepam 0.25 mg HS & Resperidone 1 mg HS. Patient defaulted on imatinib mesylate from December 2013 to April 2104. Patient underwent bone marrow biopsy & Imatinib resistance mutation analysis (IRMA) via RTPCR in August 2014 (E225V mutation in P loop domain of bcr-abl transcript) and he was started on Dasatinib 100 mg OD on September 7, 2014. Dasatninb was stopped for 12 days (October 16, 2014 to October 28, 2014) following severe drug induced dermatitis and grade I haemorrhoids. Dasatninb was restarted at a lower dose of 50 mg OD and escalated to 70 mg OD and is being currently continued. Now the patient has developed supercilliary madarosis bilaterally & diffuse cutaneous hypopigmentaion for the past 5 months. Results: The patient is currently on Dasatinib 70 mg OD, on regular follow up & The Quantitative bcr abl translocation assay revealing a transcript ratio of 0% with cutaneous hypopigmentation and bilateral Supercilliary madarosis Conclusion: Cutaneous toxicities are regarded as potential indicators of responsiveness to therapy while on treatment on TKI, because they indicate biological activity. Cutaneous side effects may adversely affect patients quality of life and, therefore require prompt attention to prompt attention to prevent long-term complications or suboptimal outcomes due to poor compliance.
A case of multiple myeloma presenting with plasmacytoma of body of sphenoid bone: A case report
Saroj Gupta Cancer Centre and Research Centre, Kolkata, West Bengal, India, E-mail: [email protected]
Introduction: Uveal melanoma is a cancer (melanoma) of the eye involving the iris, ciliary body, or choroid (collectively referred to as the uvea). The liver is a frequent site for metastasis in patients with uveal melanoma. The interval between the diagnosis of the uveal melanoma and the diagnosis of the metastatic lesion can vary. Despite therapy, the median survival of those with liver metastasis is five to seven months. Case Report: We report here a rare case of choriodal melanoma in a 45 year old Indian male smoker presented with liver metastasis within just eight months after completion of initial treatments consists of enucleation of eye and Three Dimensional-conformal radiation therapy (3D-CRT). The metastasis is an incidental finding on imaging after having some vague symptoms. This type of very early metastasis after completing initial treatment is very rare and proves the aggressiveness of the disease. Conclusion: Metastasis should be zealously sought following treatment of a primary lesion.
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