Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera.

BACKGROUND: Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory hormone hepcidin, restricts the availability of iron for erythropoiesis. The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown. METHODS: In part 1 of the international, phase 2 REVIVE trial, we enrolled patients in a 28-week dose-finding assessment of rusfertide. Part 2 was a double-blind, randomized withdrawal period in which we assigned patients, in a 1:1 ratio, to receive rusfertide or placebo for 12 weeks. The primary efficacy end point was a response, defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Patient-reported outcomes were assessed by means of the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary (scores range from 0 to 10, with higher scores indicating greater severity of symptoms). RESULTS: Seventy patients were enrolled in part 1 of the trial, and 59 were assigned to receive rusfertide (30 patients) or placebo (29 patients) in part 2. The estimated mean (±SD) number of phlebotomies per year was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). The mean maximum hematocrit was 44.5±2.2% during part 1 as compared with 50.0±5.8% during the 28 weeks before the first dose of rusfertide. During part 2, a response was observed in 60% of the patients who received rusfertide as compared with 17% of those who received placebo (P = 0.002). Between baseline and the end of part 1, rusfertide treatment was associated with a decrease in individual symptom scores on the MPN-SAF in patients with moderate or severe symptoms at baseline. During parts 1 and 2, grade 3 adverse events occurred in 13% of the patients, and none of the patients had a grade 4 or 5 event. Injection-site reactions of grade 1 or 2 in severity were common. CONCLUSIONS: In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo. (Funded by Protagonist Therapeutics; REVIVE ClinicalTrials.gov number, NCT04057040.).

Leukemia-associated aberrant immunophenotype: A flow cytometry-based experience of 110 cases from a tertiary care center in Northern India.

Background: Leukemic cells express a characteristic set of "cluster of differentiation" (CD) markers, which forms the basis of the current WHO classification. Leukemia-associated aberrant immunophenotype (LAIP) refers to expression of unusual CD markers by leukemic cells, which are not normally expressed by their respective lineage. The incidence of LAIP varies considerably, and its clinical implications, prognostic relevance, and sensitivity to therapy are still debatable. This study was conducted to identify the immunophenotypic aberrancies in newly diagnosed leukemias in our Institute. Method: This was an observational study, which included newly diagnosed leukemias on flow cytometry. Aberrant immunophenotypic expressions were recorded whenever present and were correlated with prognostic factors like age, gender, and total leucocyte count (TLC). Results: The study included 110 newly diagnosed cases of leukemias (85 acute and 25 chronic) over 1.5 years. Immunophenotypic aberrancies were detected in 40.4% of the cases. The highest incidence of aberrations was detected in acute myeloid leukemia (60.7%). LAIPs were detected in 50% of T-acute lymphoblastic leukemia and 25% cases of in B-cell acute lymphoblastic leukemia (B-ALL). Aberrant CD33 and CD56 expression in B-ALL correlated with poor prognostic factors like higher age and higher TLC, respectively. Immunophenotypic aberrancies were present in 28% cases of chronic lymphocytic leukemia. Conclusion: The results of this study have generated valuable baseline data on the incidence of LAIPs in this region. This information is vital because establishing LAIPs at the time of diagnosis is crucial for disease monitoring. Some LAIPs are associated with underlying cytogenetic abnormalities and hence impact the management and prognosis.

Derivative 6 as an additional chromosomal abnormality along with t(15;17): A case report.

Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia (AML) characterized by the presence of t(15;17)(q22;q21) translocation leading to fusion between PML and RARa gene. Treatment combining all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has dramatically improved the prognosis of APL. We report a rare finding of primary clone of t(15;17) followed by a sequential clonal evolution of additional derivative chromosome 6 formation by a two hit mechanism. Our case showed a good clinical response with a four years and nine months event free survival after ATRA and ATO combination therapy in spite of existence of three chromosomal abnormalities stating that targeted therapy overcomes the adverse effects of additional genetic markers. However, close monitoring with assessment for long term prognostic behavior is required.

A sequential exploratory study to develop and validate neutropenic nursing care bundle for neutropenic patients admitted in a tertiary care hospital, Uttarakhand.

BACKGROUND: Patients diagnosed with cancer and who undergo cancer treatment are at potential risk of bone marrow suppression leading to prolonged hospitalization, delay in treatment, and chemotherapy dose reductions, which ultimately results in significant morbidity and mortality. This sequential exploratory study using a mixed-method approach was aimed to develop and validate a neutropenic nursing care (NNC) bundle for neutropenic patients admitted in a tertiary care hospital, Uttarakhand. MATERIAL AND METHODS: This sequential exploratory study design with an instrument developmental model was used to develop the NNC bundle. It consisted of two phases: Qualitative phase and quantitative phase. In the qualitative phase, focused group discussion with eight oncology nurses was performed to derive themes related to neutropenic nursing care using conventional content analysis. An extensive literature review was also performed on these themes to explore the current pieces of evidence for item pool generation. In the quantitative phase, a preliminary draft bundle was developed, and two Delphi rounds (I and II) were carried out among the five experts for the content validation of the NNC bundle and a final bundle was developed. RESULTS: Major domains identified for the bundle were hand hygiene, care of central and peripheral lines, routine oral care, antiseptic bath, peri-anal care, diet, and environmental hygiene. The content validity index (CVI) of the bundle was found to be >80% for all the items with I-CVI >0.8 and S-CVI = 0.99 after conducting two rounds of Delphi. CONCLUSION: The present study has provided a set of valid written neutropenic nursing interventions to prevent complications in neutropenic patients. The NNC bundle should be subjected to other levels of evaluation that measure the bundle's practicability and suitability for the intended field.

Diffuse large B-cell lymphoma and new insights into its pathobiology and implication in treatment.

The most common non-Hodgkin lymphoma (NHL) subtype is diffuse large B-cell lymphoma (DLBCL). It accounts for roughly 30% of all cases of NHL affecting both nodal and extra nodal sites. There are molecular subtypes of DLBCL, germinal centre subtype (GCB), and activated B-cell (ABC), based on gene expression profiling (GEP), in accumulation to distinct morphological and clinicopathological subtypes. To prognosticate patients, the International Prognostication Index (IPI) and its variants are used. In ABC type DLBCL, limited stage disease is treated with a combination of abbreviated systemic chemotherapy (three cycles) and field radiation therapy. Although advanced stage disease is treated with a full course of chemotherapy as well as novel agents (Bortezomib, Ibrutinib, Lenalidomide). In this review study, we looked at the role of multiple aspects of genetic and microenvironment changes which have effects in DLBCL tumours.

Hepatic Plasmacytoma With DEL13q14 Positive on Fluorescent In Situ Hybridization (FISH) on Tissue Biopsy.

A 40-year-old male presented with abdominal distension and dyspnea. On evaluation found to have hepatic plasmacytoma without marrow clonal plasma cells. Fluorescent in situ hybridization (FISH) on tissue biopsy revealed myeloma-defining cytogenetics. After treating with novel agents, the patient had a complete response to therapy.

Quality of life and factors affecting it in adult cancer patients undergoing cancer chemotherapy in a tertiary care hospital.

BACKGROUND: Cancer is the second most common cause of deaths worldwide. Likewise, in India, it is a major health problem, and disease burden is escalating every year. Cancer chemotherapy produces unfavorable effects on the well-being of an individual. Since the past few years, quality of life (QoL) is considered as the main goal of cancer treatment in the survival of a patient. AIM: This current study aimed to assess the QoL and factors affecting it in adult cancer patients undergoing chemotherapy treatment. METHODS AND RESULTS: An analytical, cross-sectional study was conducted to achieve the objectives, employing the consecutive sampling method. A total of 120 adult (>19 years) patients were recruited from daycare chemotherapy unit of a tertiary care hospital. The data were collected using patient record form and Functional Assessment of Cancer Therapy-General (FACT-G), a quality of life (QoL) questionnaire. The overall mean score of quality of life (QoL) was 61.933 ± 5.85502. The domains of functional well-being and emotional well-being were most negatively affected after cancer chemotherapy. Education (illiteracy) and occupation (unemployment) were negatively associated with overall quality of life (QoL) of cancer patients on chemotherapy. Adverse drug reactions due to cancer chemotherapy negatively affect the quality of life (QoL) of cancer patients. Education (illiteracy) affects social well-being domain of cancer patients. Working in the government/private sector has a positive impact on functional well-being domain of quality of life (QoL). CONCLUSION: The study findings suggest an overall low quality of life (QoL) among adult cancer patients undergoing chemotherapy at our setup. It has been identified as a stressful therapy, also affecting both psychological and physical well-being. Poor infrastructure, illiteracy, poverty, and lack of proper treatment facilities at most centres often lead to poor survival outcomes and hence focus has always been on achieving quantity of life rather than quality of life (QoL). This is further complicated due to nonavailability of validated tools in local vernacular, apathy of the treating physicians in the context of QoL aspects and social and cultural factors that are unique to this society. Psycho-oncology needs to become an integral entity of comprehensive cancer care.

Frequency, nature, severity and preventability of adverse drug reactions arising from cancer chemotherapy in a teaching hospital.

BACKGROUND: An adverse drug reaction (ADR) is defined by the World Health Organization (WHO) as "Any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis or therapy". Cancer chemotherapy is associated with the occurrence of ADRs, which is a worldwide problem. Monitoring and reporting of these ADRs are essential to safeguard the patient and to manage it accordingly. The outcome would create alertness and prevent their recurrence. Hence, we have undertaken a hospital-based study to study the frequency and nature of ADRs due to chemotherapeutic agents. METHODS: A total of 500 patients developed ADRs due to cancer chemotherapy from 13th April 2018 to 18th September 2019. Demographics of the patient, drugs taken, and ADRs encountered were recorded in a predesigned form. RESULTS: A total of 665 ADRs were recorded from 500 patients. Anemia was the most common ADR encountered followed by nausea/vomiting and leucopenia. Leukemia (s) were common cancer observed followed by lung and breast cancers. The most common drugs implicated were cisplatin, paclitaxel, carboplatin, and doxorubicin. Naranjo's scale showed 92% of ADRs as probable and 7% as possible. Severity scale showed 80.2% of ADRs were of moderate (level 3 and 4) severity, 11.6% of mild (level 1 and 2) severity, and 8.2% of level 5 severity. A total of 26.8% of ADRs were deemed preventable and 73.2% were not preventable. CONCLUSIONS: Our study provides safety data regarding the usage of anti-cancer drugs. Hence, it creates alertness among the treating doctors to prevent its recurrence.

Clinico-hematological study of pancytopenia: A single-center experience from north Himalayan region of India.

BACKGROUND: Pancytopenia, an important hematological presentation is associated with different causes, which may vary in different regions. Uttarakhand, a north Himalayan state of India lacks studies of pancytopenia and the prevalent causes present in this region. Therefore, the present study was conducted to study the clinico-hematological profile of pancytopenia in a tertiary care center in the Uttarakhand, a north Himalayan state of India. It was also intended to study if these causes showed any variation from other studies done in different regions of India. MATERIALS AND METHODS: The present observational study was conducted in a tertiary care institute situated in Uttarakhand state of India over a period of 1 year and 8 month from June 2017 to Feb 2019 including all the cases of pancytopenia. RESULTS: The most common cause of pancytopenia was megaloblastic anemia (25%), followed by aleukemic leukemia and hypoplastic/aplastic anemia (19.1% each). Visceral leishmaniasis also constituted an important cause of pancytopenia in this study (11.7%). CONCLUSION: The study concludes that megaloblastic anemia and aleukemic leukemia are the most common cause of pancytopenia. Although leishmaniasis is considered to be non-endemic in this region, it constitutes an important cause of pancytopenia here. The clinicians, especially the physicians practicing the primary care and pathologists, should be aware of the different causes of pancytopenia present in this Himalayan region of India; therefore, delay in diagnosis can be prevented along with unnecessary investigations.

A prospective, randomized study to compare the combination of imatinib and cytarabine versus imatinib alone in newly diagnosed patients with chronic phase chronic myeloid leukemia.

INTRODUCTION: To compare the efficacy and safety of imatinib and cytarabine (ara-c) combination versus imatinib monotherapy in newly diagnosed patients with chronic phase chronic myeloid leukemia (CML-CP). MATERIALS AND METHODS: This prospective, randomized study included adult patients (age >18 years) with newly diagnosed CML-CP. Patients received either a single oral dose of imatinib 400 mg/day in combination with a subcutaneous injection of ara-c 20 mg/m2/day (imatinib + ara-c) or a single oral dose of imatinib 400 mg/day. Primary endpoints were hematological and molecular responses at 3 months and cytogenetic responses at 6 and 12 months. Secondary endpoints included grade 3/4 hematological and nonhematological adverse events (AEs). RESULTS: Of 30 patients included, 14 were randomized to imatinib + ara-c and 16 to imatinib alone. Complete hematologic response (CHR) at 3 months was higher with imatinib + ara-c vs. imatinib alone (100% vs. 87.5%, P = 0.48). The median time to achieve CHR was significantly (P < 0.001) lower with imatinib + ara-c (32.07 vs. 23.43 days). Molecular response at 3 months was significantly higher (P = 0.04) with imatinib + ara-c vs. imatinib alone (100% vs. 68.75%). Complete cytogenetic response was also higher with imatinib + ara-c vs. imatinib alone (42.85% vs. 25% at 6 months and 71.4% vs. 62.5% at 12 months). Neutropenia followed by thrombocytopenia and anemia were the most common AEs. Grade 3/4 hematological and nausea events were significantly (P < 0.05) higher with imatinib + ara-c. Other nonhematological events were not significantly different between the treatments. The median follow-up duration was 20 months (range: 15-23 months). CONCLUSION: Imatinib with low-dose ara-c can be considered as a potential first-line treatment option for CML-CP.