The limited use of autologous hematopoietic stem cell transplant for fit older patients with multiple myeloma in India: a retrospective analysis.

BACKGROUND: Multiple myeloma (MM) predominantly affects older patients; many of whom do not undergo autologous hematopoietic stem cell transplant (AHSCT) despite the associated survival benefits. This study was conceived to investigate the patterns of AHSCT among MM patients with due regard to their age and standardized fitness assessments. METHODS: Fitness scores as per the hematopoietic stem cell transplant-comorbidity index (HSCT-CI) and risk scores as per the revised-myeloma comorbidity index (R-MCI) of MM patients treated between January 2017 and December 2019 were analyzed to assess fitness for AHSCT. Proportions of patients who underwent AHSCT were calculated with regard to age and fitness for AHSCT. RESULTS: Of the 81 eligible patient records with a median age of 62 years, the HSCT-CI classified 79.6% and 77.8% of patients aged ≤65 years and >65 years as AHSCT eligible (p 1). Using the R-MCI, 96.3% and 81.5% of patients aged ≤65 years and >65 years, respectively, were classified as eligible for AHSCT (p 0.0381). Overall, patients aged ≤65 years underwent AHSCT with a greater frequency compared to those aged >65years (38.9 vs. 14.8%, p 0.0402). Irrespective of the age group, there was a statistically significant difference (p 0.0167) in terms of survival which favored those who underwent AHSCT. CONCLUSIONS: Both the HSCT-CI and the R-MCI revealed that nearly 80% of patients aged >65 years were fit enough to receive AHSCT. However, far fewer patients of this age group underwent AHSCT. We propose that the routine inclusion of objective fitness assessment could ensure that fit older patients undergo AHSCT and thus do not miss out on the benefits of the same.

A potential role for cyclophosphamide in the mitigation of acute respiratory distress syndrome among patients with SARS-CoV-2.

While humanity struggles to develop a vaccine against SARS-CoV-2, it is imperative that effective and affordable therapeutic strategies be evolved. Since a majority of the SARS-CoV-2 deaths are due to acute respiratory distress syndrome (ARDS), a strategy to mitigate the same could save countless lives. Since SARS-CoV-2 related ARDS has a strong immunological component, many investigators are utilizing monoclonal antibodies against IL-6, TNF-alpha and CCR5. However, targeting a single cytokine with an expensive monoclonal antibody could be a less pragmatic approach. We propose the use of cyclophosphamide as an immunomodulator, given its proven role in various settings including autoimmune diseases, and in the post-haploidentical stem cell transplant. Cyclophosphamide could deplete cytotoxic and effector T cell populations while relatively sparing the regulatory T cells (Tregs). Cyclophosphamide could tip the balance away from the overtly pro-inflammatory and could be a less expensive and effective alternative to the currently investigated monoclonal antibodies.

Sanctuary site central nervous system relapse-refractory DLBCL responding to nivolumab and lenalidomide.

Despite improvement in survival in diffuse large B-cell lymphoma (DLBCL) with the introduction of rituximab, central nervous system (CNS) relapse continues to represent a clinical challenge. In diffuse large B-cell lymphoma (DLBCL), the incidence of CNS relapse is only ∼5% in unselected cohorts. Immunotherapy is the treatment that either boosts the patient's own immune system or uses man-made versions of the normal parts of the immune system to kill lymphoma cells or slow their growth. We are presenting a thirty-eight year old man who, presented with neck nodes, axillary nodes, altered sensorium, abnormal body movements, unconsciousness, weight loss and, fever, with a past history of DLBCL in May 2008, treated with 6 cycles of CHOP and completed in November 2008. After 9 years in April 2018, the patient developed similar symptoms and treated with salvage chemotherapy with R-DHAP which was completed in September 2018. Post-treatment PET-CT showed partial metabolic response and we started external beam radiotherapy to initial bulky disease. After completion of radiotherapy, the patient was very reluctant for any type of therapy and went home. After one month he presented to us with persistent vomiting, abnormal body movements and, altered sensorium. On examination, his Glasgow Coma Scale (GCS) was E2V3M2 and he was admitted in Intensive Care Unit. The patient was managed with mannitol, dexamethasone, antiepileptics, antibiotics and other supportive care medicines. His brain magnetic resonance imaging (MRI) was showing multiple heterogeneously enhancing lesions with surrounding vasogenic oedema and his cerebrospinal fluid analysis was positive for malignant cells. He was managed with triple intrathecal chemotherapy with methotrexate 12 mg, Cytarabine 50 mg, and Hydrocortisone 50 mg along with other supportive care medicines, and after 4-5 days he regained consciousness and he was able to talk and understand verbal commands. In view of improvement in general condition and performance status, we started biweekly triple intra-thecal therapy, and Inj. Nivolumab 3 mg per kg q 2 weekly. From the second cycle, we started Lenalidomide 10 mg once a day for 21 days with 7 days gap along with 2 weekly nivolumab and biweekly triple IT chemotherapy. After one month his CSF analysis was negative for malignant cells. Now he is on regular treatment with weekly IT chemotherapy, 2 weekly nivolumab and 3 weeks on and one week off lenalidomide. After 2 months of treatment, his MRI Brain was showing. At the time of submission of this article, he has completed the fifth cycle of immunotherapy and two cycles of lenalidomide. He was able to manage his daily ADL and able to walk with a stick. The patient tolerated immunotherapy, triple IT therapy and lenalidomide very well without much intolerable side effects. Therefore, we concluded that nivolumab and lenalidomide was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory sanctuary site CNS B- cell lymphomas. Additional studies of Nivolumab and lenalidomide in these diseases are ongoing.

Primary Vaginal Chloroma: A Rare Case Report.

Chloroma (granulocytic sarcoma or myeloid sarcoma) is a rare malignant extra-medullary neoplasm of myeloid precursor cells. It is usually associated with myeloproliferative disorders but very rarely may precede the onset of leukaemia. Here we are presenting a rare case of chloroma in a female patient without initial presentation of AML. 38 year old female patient, with performance score-1 had complaining of per vaginal bleeding for 1-2 days. Patient consulted gynaecologist and underwent biopsy from anterior fornix of vagina. Biopsy material was positive for LCA (leukocyte common antigen), MPO (myeloperoxidase), c-kit positive on IHC (immunohistocytochemistry) while negative for cytokeratin, synaptophysin, chromogranin, CD20 (cluster of differentiation. Whole body CT scan was non informative except mass lesion at vagina. Patient was given 3+7 induction chemotherapy which was tolerated well followed by high dose cytarabine as consolidation therapy.

Hepatosplenic Gamma Delta T-Cell Lymphoma (HSGDTCL): Two Rare Case Reports from Western India.

Peripheral T cell lymphomas are a heterogeneous group of post-thymic, mature lymphoid malignancies, accounting for approximately 10-15% of all non-Hodgkin's lymphomas. Hepatosplenic T-cell lymphoma (HSGDTCL) is a rare entity, which is characterized by primary extra nodal disease with typical sinusoidal or sinusal infiltration of the liver and the spleen, respectively by expression of the T-cell receptor Î³Î´ chain, and by a number of other frequent clinicopathologic features, including aggressive course of disease. Secondary involvement of liver by hematopoietic malignancies is much more common as compared to primary liver involvement. Primary involvement of liver by non- Hodgkin's lymphoma (NHL) is documented and mostly DLBCL (diffuse large B cell lymphoma) type. But, T cell lymphoma primarily arising from liver is very rare. It occurred commonly in immunocompromised patients and prognosis is very poor. Here, we present two case reports of Hepatosplenic gamma-delta T-cell lymphoma (HSGDTCL) and both are immunocompetent patients. Liver biopsy from the mass and subsequent IHC (immunohistochemistry) were performed for the purpose of diagnosis, which were positive for LCA (leukocyte common antigen), CD2 and negative for CD5, CD20 and CD79a. First patient was a 63-year-old female with hepatitis C virus seropositivity presented with liver mass simulating hepatocellular carcinoma. Second patient was a 60-year- old male, chronic alcoholic patient, presented with liver mass and lytic bony lesion in pelvis. Both patients were managed with conventional CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone) and showed complete response after 4 cycles of chemotherapy. After completion of 6 cycles of chemotherapy, both patients remained under 6-month surveillance period for any recurrence of the disease.

Role of benzydamine hydrochloride in the prevention of oral mucositis in head and neck cancer patients treated with radiotherapy (>50 Gy) with or without chemotherapy.

PURPOSE: Benzydamine is recommended for prophylaxis of oral mucositis (OM) in head and neck cancer (HNC) patients for radiation doses (<50 Gy). This study evaluates role of benzydamine for higher radiation doses (>50 Gy) with or without chemotherapy. METHODS: One hundred twenty patients of HNC with planned radiation doses of ≥60 Gy were randomized to group A (control radiotherapy alone), group B (study radiotherapy alone), group C (control chemoradiotherapy), or to group D (study chemoradiotherapy). Groups A and C were advised saline mouth rinses, and in groups B and D, additional benzydamine rinses (0.15%) were advised. Mucositis grading was done with both WHO (WHO-M) and CTCAE (CTC-M) version 4.0 (common terminology criteria for adverse events) weekly. RESULTS: Patient characteristics are presented in the table. Patients in group B had lesser grade 3 WHO-M and CTC-M as compared to group A, 62.1 vs. 36.4% (p = 0.038) and 51.7 vs. 27.3% (p = 0.043), respectively. The rates of Ryle's tube feeding (RTF), intravenous fluid supplementation (IVF), and hospitalization were also lesser in group B as compared to A, 34.5 vs. 21.2% (p = 0.18), 27.6 vs. 9.1% (p = 0.06), and 6.9 vs. 0% (p = 0.21), respectively. WHO-M and CTC-M in groups C and D were not statistically different, 64.3 vs. 43.3% (p = 0.091) and 53.6% vs. 43.3% (p = 0.30), respectively. The rates of RTF, IVF, and hospitalization were all lesser but p > 0.05. CONCLUSION: Benzydamine significantly reduces OM even at doses >50 Gy in HNC patients. Its role in patients receiving concurrent chemotherapy further needs to be evaluated.

Can pure accelerated radiotherapy given as six fractions weekly be an option in locally advanced carcinoma cervix: Results of a prospective randomized phase III trial.

CONTEXT: Concurrent chemoradiation is presently the standard of care in locally advanced malignancy of the cervix uteri. But accelerated radiotherapy regimes have not been investigated much. AIMS: We conducted a randomized trial to compare the results of pure accelerated radiotherapy given as six fractions weekly to standard chemoradiotherapy in locally advanced carcinoma cervix patients. SETTINGS AND DESIGN: This was a prospective, phase III trial in which 106 patients of locally advanced (stage II and III) carcinoma cervix were randomized into two arms. SUBJECTS AND METHODS: The study arm (ART) received 50 Gy accelerated radiotherapy in 25 fractions, six fractions weekly; while control (CRT) arm was treated with concurrent chemoradiation 50 Gy in 25 fractions with weekly injection cisplatin. This was followed by intracavitary brachytherapy (ICBT; total dose of 85 Gy to point A) in both the arms. Fifty-one patients completed treatment in the ART arm and 50 patients in the CRT arm. In these patients, response to treatment, toxicity, and overall survival (OS) and disease-free survival (DFS) were compared between both the arms. STATISTICAL ANALYSIS USED: Survival analysis was done using Kaplan.Meier estimates, logrank test was used to compare differences, while proportions were compared using the Fisher's t-test. RESULTS: At a median follow.up of 36. months there was no difference between the two arms in terms of OS. (61 vs 62%,P = 0.9009) as well as DFS. (60 vs 64%,P = 0.6411) CONCLUSIONS: Accelerated radiotherapy given as six fractions per week is an effective alternative to concomitant chemoradiation in locally advanced carcinoma cervix and has shown lesser toxicities in our study.

Molecular targeted therapy to improve radiotherapeutic outcomes for non-small cell lung carcinoma.

Effective treatments for non-small cell lung carcinoma (NSCLC) remain elusive. The use of concurrent chemotherapy with radiotherapy (RT) has improved outcomes, but a significant proportion of NSCLC patients are too frail to be able to tolerate an intense course of concurrent chemoradiotherapy. The development of targeted therapies ignited new hope in enhancing radiotherapeutic outcomes. The use of targeted therapies against the epidermal growth factor receptor (EGFR) has offered slight but significant benefits in concurrent use with RT for certain patients in certain situations. However, despite theoretical promise, the use of anti-angiogenics, such as bevacizumab and endostatin, has not proven clinically safe or useful in combination with RT. However, many new targeted agents against new targets are being experimented for combined use with RT. It is hoped that these agents may provide a significant breakthrough in the radiotherapeutic management of NSCLC. The current review provides a brief discussion about the targets, the targeted therapies, the rationale for the use of targeted therapies in combination with RT, and a brief review of the existing data on the subject.

Chemically enhanced radiotherapy: visions for the future.

Radiotherapy (RT) is an important part of cancer management, with more than a third of all cancer cures being attributable to RT. Despite the advances in RT over the past century, the overall outcomes in a majority of malignancies are still unsatisfactory. There has been a constant endeavor to enhance the outcome of RT, and this has been in the form of altered fractionation, oxymimetic radiosensitizers, the use of concurrent chemotherapy, anti-angiogenic therapy and anti-growth factor receptor targeted therapies. This article presents a vision for the future, with emphasis upon emerging prospects which could enhance RT outcomes. Positive speculations regarding the use of immunological aspects, the use of nanoscale technology and the adoption of metronomic concurrent chemotherapy have been presented. Also, the potential with the use of low dose hyperradiosensitivity in enhancing chemotherapy outcomes too has been discussed. In this era of evidence based clinical practise, there exists a strong obsession towards the 'present' with 'contempt towards the future'. Accepting the shortcomings of the existing modalities, there must be a strong zeal towards discovering better methodologies to enhance radiotherapeutic outcomes for the sake of a better future.

Radiotherapy to volumes defined by metabolic imaging in gliomas: time to abandon monstrous margins?

The survival in patients with high grade gliomas (HGG) remains poor even after the adoption post-operative radiotherapy (RT) to magnetic resonance imaging (MRI) based volumes. Despite delivery of 'standardized' doses of radiation, recurrence is the norm, rather than the exception. Recurrences occur both within, and outside of the volume of irradiation, leading us to two questions-firstly concerning the adequacy of the dose of radiation used, and secondly about the current methods of treatment volume delineation. The emergence of newer radiopharmaceuticals for use in positron emission tomography (PET) have kindled the hope of more precise volume localizations for post-operative RT, and it is likely that these new radiopharmaceuticals can help us define accurate areas at highest risk of recurrence and thus allow us to use increased doses of radiation with confidence.

The results with the addition of metronomic cyclophosphamide to palliative radiotherapy for the treatment of non-small cell lung carcinoma.

BACKGROUND: A considerable proportion of non-small cell lung carcinoma (NSCLC) patients are ineligible for radical therapies. Many are frail not to tolerate intravenous palliative chemotherapy either. These patients often receive palliative radiotherapy (RT), or supportive care alone. We intend to compare outcomes with palliative RT alone, versus palliative RT plus oral low dose metronomic cyclophosphamide. METHODS: Data was mined from 139 eligible NSCLC patient records. Comparisons were made between 65 patients treated from January 2011 to March 2013 with palliative RT (20-30 Gray in 5-10 fractions) alone, versus 74 patients treated from April 2013 to December 2014 with palliative RT plus oral metronomic cyclophosphamide (50 mg once daily from day of initiation of RT until at least the day of disease progression). Response was assessed after 1-month post-RT by computed tomography. Patients with complete or partial response were recorded as responders. For the determination of progression free survival (PFS), progression would be declared in case of increase in size of lesions, development of new lesions, or development of effusions. The proportions of responders were compared with the Fisher exact test, and the PFS curves were compared with the log-rank test. RESULTS: Differences in response rates were statistically insignificant. The PFS was significantly higher when metronomic chemotherapy was added to RT in comparison to treatment with RT alone (mean PFS 3.1 vs. 2.55 months; P=0.0501). Further histological sub-group analysis revealed that the enhanced outcomes with addition of metronomic cyclophosphamide to RT were limited to patients with adenocarcinoma histology (3.5 vs. 2.4 months; P=0.0053), while there was no benefit for those with squamous cell histology (2.6 vs. 2.6 months; P=1). At the dose of oral cyclophosphamide used, there was no recorded instance of any measurable hematological toxicity. CONCLUSIONS: For pulmonary adenocarcinoma patients, the treatment with palliative RT plus oral metronomic cyclophosphamide is better than that with palliative RT alone. However, for pulmonary squamous cell carcinoma the addition of oral metronomic cyclophosphamide to palliative RT offered no benefit. Further studies with similar and different metronomic chemotherapy agents are justifiable.