Chronic Myeloid Leukaemia Presented with Extreme Isolated Thrombocytosis

CML presenting with isolated extreme thrombocytosis is rare. We reported a 47 years old man who presented with history of right sided lower abdominal pain, vomiting, significant lethargy and chest tightness. Patient was mildly anaemic and abdominal examination revealed no organomegaly. On investigation, he was found to have extreme thrombocytosis (2050x109/L) and mild leucocytosis (31.7 x109/L) with mild anaemia. In view of extreme thrombocytosis, he was investigated for myeloproliferative disease especially essential thrombocythemia. He was found to be positive for BCR-ABL by reverse transcription PCR (RT-PCR) and negative for JAK2, CALR, MPL mutations. Ultimately, he was diagnosed as a case of CML with an atypical presentation. He received imatinib 400 mg/day and achieve complete haematological response at 15 days.

Studies on the Quantification of Mutation Resistance to Specific Drug Therapy in Chronic Myeloid Leukemia patients

Imatinib is a type of protein tyrosine kinase inhibitor which inhibits the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome i.e. the BCR-ABL tyrosine kinase, abnormality in CML patient. The aim of the study is to assess the response of imatinib in CML patients and to observe resistance to imatinib. Study was performed at Ahmedabad, Gujarat, India. Dose of 400, 600, 800 mg of Imatinib was found to be prescribed to all patients during the study. Comparison of laboratory parameters and PCR data were done after measurement by RT-PCR method. Total 256 patients with CML were enrolled in the study. 196 patients had completed study as per protocol. 38 patients were newly diagnosed whereas 158 patients were already diagnosed with CML. 89.29% (n = 175) of patients achieved complete haematological response, Complete MolR were achieved in n = 41 at 6th months, n = 1 at 12th month and 18th month and no patient was found with none CyR out of 196 patients; no patient were found with minimal CyR at 6th month, 2 patient were at 12th month and 3 patients were at 18th month. Mean PCR value (BCR-ABL/ABL ratio) in patient was found 0.245±1.16 at Day 0, 0.824±1.51 at 6th month, 4.086±9.58 at 12th month and 6.713±11.32 at 18th month visit. In conclusion, it was observed that resistance to imatinib might be developed within an average time of 12 months in the patients due to which survival rate was drastically reduced.

Resolution of primary hepatic marginal zone lymphoma in a hepatitis C virus-infected patient treated with a direct-acting antiviral

ABSTRACT The favorable impact of antiviral therapy on low-grade hepatitis C virus (HCV)-related non-Hodgkin lymphoma manifesting as marginal zone lymphoma (MZL) has been reported in some clinical studies. However, primary HCV-related marginal zone lymphomas (MZLs) confined to the liver have not been described in the literature nor have the resolution of liver lymphoma through anti-HCV eradication treatment. The authors report a genotype 1b HCV-positive patient with chronic hepatitis who exhibited lesions involving both hepatic lobes resembling hepatocellular carcinoma. Liver biopsy revealed an MZL of the liver. Antiviral treatment using sofosbuvir associated with simeprevir as unique treatment was started and resulted in complete haematological response. In HCV-related MZL isolated to the liver, antiviral treatment has led to the eradication of viral infection and a complete haematological response. Antiviral therapy should be considered as a first-line treatment for HCV-related primary MZLs of the liver.

Response of factor X deficiency to darutumumab in the treatment of AL amyloidosis: a novel finding

We report a case of progressive light-chain amyloidosis (otherwise known as AL amyloidosis) with acquired factor X (aFX) deficiency with a complete haematological response and rapid normalisation of FX levels following daratumumab monotherapy. To our knowledge, this is the first case report documenting successful treatment with daratumumab of aFX deficiency secondary to AL amyloidosis. The patient responded well to this therapy, with excellent symptomatic and quality of life improvements as well as a reduction in bleeding manifestations. This case highlights the value in considering daratumumab treatment when AL amyloidosis is complicated by FX deficiency.

Polycythaemia following treatment of lymphoplasmacytic lymphoma

A 61-year-old man presented to the department of clinical haematology in February 2016 with symptomatic anaemia, generalised lymphadenopathy and hepatomegaly. Routine investigations showed severe anaemia with the presence of lymphoplasmacytoid cells in the peripheral smear, and bone marrow examination with IHC and serum protein electrophoresis confirmed diagnosis of lymphoplasmacytic lymphoma. The patient received supportive transfusion therapy and combination chemotherapy. After VI cycles, the patient had a complete haematological response with marrow in remission. Maintenance rituximab was planned every 3 months for 2 years. At the time of first dose of maintenance rituximab, his haemoglobin (Hb) was 189 g/L with low normal erythropoietin level. During the last 3 years follow-up, his Hb ranged between 16.5 and 20.1 g/dL. All causes of secondary polycythaemia were ruled out. Workup for polycythAemia vera (PV), including JAK-2 and bone marrow, was not suggestive of PV. We labelled it as a case of polycythaemia due to undetermined aetiology.

Complete haematological response to Imatinib in chronic myeloid leukaemia patients attending the Ocean Road Cancer Institute in Tanzania

Background: There is limited information on clinical characteristics, diagnosis and response to therapy of patients with chronic myeloid leukaemia (CML) in Tanzania. This hospital-based retrospective and cross-sectional study was conducted to describe the clinical and laboratory characteristics, time to diagnosis and response to first line therapy with imatinib in Philadelphia chromosome positive CML.Methods: The study was conducted at the Ocean Road Cancer Institute in Dar es Salaam, Tanzania. Participants were sequentially recruited from the outpatient clinic where a structured questionnaire was employed seeking details socio-clinical features of the disease. Haematology indices at baseline and at three months of treatment was obtained from patient’s medical records. Haematological response was determined at three months of imatinib use using leukaemia net definition.Results: Of 127 study participants, 63% were males. The mean (±standard deviation) age at diagnosis was 40 (±16) years, majority being in the third decade of life. Abdominal distention (88%) and symptoms of anaemia (84%) were the most frequent complaints. Splenomegaly (92%) and pallor (82.7%) were the common physical findings. The mean duration from consultation to diagnosis was 3(±0) weeks and mean duration from diagnosis to imatinib therapy initiation was 3 (±0.9) weeks. A total of 116 (91.3%) of patients had complete haematological response to imatinib therapy three months after therapy. There was significant decline in total white blood cell counts, basophils count, platelets and increase in haemoglobin at three months after imatinib therapy initiation.Conclusion: Majority of patients were young with clinical and laboratory findings of severe disease. Patients presented late to hospital and there was a considerable long time to reach a final diagnosis and yet haematological response was still achieved in majority of these patients with imatinib therapy. The elucidated clinical and laboratory findings should advocate early CML diagnosis and immediate referral to a tertiary hospital.

Major molecular response induced by nilotinib as first line treatment in a LMC patient with intermediate Sokal risk

Here we describe a case of a man with chronic myeloid leukemia at intermediate risk, according to the Sokal index. After cytoreduction with hydroxyurea, the patient started nilotinib at standard dose (600 mg/day) obtaining a complete haematological response after one month of treatment.After about 3 months the patient presented a complete cytogenetic response and after six months major molecular response (MR3). At nine months of treatment the patient presented a complete molecular response (MR4).

Treatment with Imatinib in Very Elderly (> 75 Years) CML Patients.

Median age of patients with CML is about 65 years, according to SEER 2000–2005 data. However, the treatment with Imatinib in elderly has been seldom specifically addressed: in particular, there is a lack of data regarding very elderly CML patients. To highlight peculiar aspects of toxicity and efficacy of Imatinib in this subset which accounts for at least 10–15% of all CML cases, we revised retrospectively 28 CML patients treated with Imatinib when aged > 75 years from 4 haematological Institution in Rome; there were 12 males and 16 females, median age at Imatinib was 78.7 years (IR 75.8 – 82.9), Sokal Risk at diagnosis was intermediate in 20 patients, high in 6 and not valuable in 2. One or more concomitant diseases requiring specific treatments were present in 26/28 patients (92.8%), with 15 patients (53.5%) assuming 3 or more concomitant drugs. Nine patients (32.1%) have been pretreated ≥ 6 months with HU before starting Imatinib; on the whole, median time from diagnosis to Imatinib was 1.8 months (IR 0.7 – 25.1). Starting dose of Imatinib was 400 mg/day in 23 patients (82.1%) and 300 mg/day in 5 patients (17.9%); overall, 15 patients (53.5%) (14/23 at 400 mg starting dose and 1/5 at 300 mg starting dose) needed a dose reduction and 6 (21.4 %) discontinued Imatinib for toxicity (early toxicity in 4 and late toxicity in 2). Excluding the 4 patients who discontinued Imatinib due to early toxicity, maximum tolerated daily dose during treatment was 400 mg in 8 patients, 300 mg in 13 patients and 200 mg in 3 patients. According to CTC-AE, grade 3 – 4 haematological and extra-haematological toxicities were observed in 7 (25%) and 12 (42.8%) patients, respectively; 2 patients (7.1%) presented a pleural effusion during Imatinib treatment. All patients were fully evaluable for response to Imatinib, with a median treatment period of 30.6 months (IR 15.7 – 49.2); six patients (21.4%) failed any response, (including 4 patients who discontinued Imatinib due to early toxicity) and 22 (78.6%) achieved a complete haematological response (CHR). Among these 22 patients in CHR, 4 refused any other karyotipic or molecular evaluation (3 are still alive in CHR, 1 died in CHR from unrelated cause after 44,5 months) and 17/18 (60.7% of all 28 patients) achieved a cytogenetic response (CyR), major in 1 patient and complete in 16 patients. In addition, 7 patients (25% of all 28 patients) achieved a complete molecular remission, with an undetectable BCR/ABL hybrid gene at qualitative nested PCR. In conclusion, Imatinib at reduced daily dose of 300 mg seems a relatively safe and quite effective treatment for very elderly CML patients; from our data, no upper age limit should be given for TKinhibitors treatment but also very elderly (and with concomitant severe diseases) patients should have this chance of cure.