Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia: A literature review.

Acute myeloid leukemia (AML) in older adults differs biologically and clinically from that in younger patients and is characterized by adverse chromosomal abnormalities, stronger intrinsic resistance, and lower tolerance to chemotherapy. In patients over age 60 with AML, cure rates are under 10% despite intensive chemotherapy, and most of them die within a year of diagnosis. Over the last decade, metronomic chemotherapy has emerged as a potential strategy to control advanced/ refractory cancer. Here, we report a case of a 68‑year‑old gentleman having AML with high‑risk cytogenetic features, who achieved complete remission on our oral metronomic PrET (PrET: Prednisolone, etoposide, thioguanine) protocol on an outpatient basis. He was later treated with standard high‑dose (HD) cytosine arabinoside (Ara‑C) consolidation followed by maintenance with etoposide, thioguanine, and sodium valproate. Presently, the patient is nearly 35 months since diagnosis and 21 months off treatment. This case report and review highlights that the combination of oral low‑intensity metronomic therapy, followed by standard HD consolidation therapy and metronomic maintenance therapy may be well tolerated by elderly patients especially with less proliferative, high (cytogenetic)‑risk AML who are otherwise deemed to be unfit for intensive intravenous induction chemotherapy regimens. References for this review were identified through searches of Pubmed for recent publications on the subject as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.

Fludarabine in lymphoproliferative malignancies: a single-centre experience.

BACKGROUND: Fludarabine has been reported to be an effective drug for the treatment of chronic lymphocytic leukaemia (CLL) and indolent lymphomas. However, its safety and efficacy in Indian patients has not been studied. We retrospectively analysed our experience with fludarabine in low grade lymphomas and CLL. METHODS: The records of all patients with low grade lymphoma or CLL who received fludarabine between April 1999 and November 2006 were analysed. Response evaluation was done as per the National Cancer Institute-Working Group guidelines for CLL and International Workshop criteria for non-Hodgkin lymphomas, respectively, in those patients who received at least 3 cycles of fludarabine. Toxicity was graded as per the common terminology criteria for adverse events, version 3.0. Median event-free survival was obtained using Kaplan-Meier survival analysis. RESULTS: Forty-seven patients were included in the study and 189 cycles were administered (median: 4 cycles per patient). Sixteen patients had a treatment delay, 14 due to myelosuppression. Twenty-five patients had low grade lymphoma and 22 had CLL. The response was evaluable in 22 patients with low grade lymphoma and 20 with CLL. The overall response rate for CLL was 100% in those treated upfront (n=9) and 55% in those with relapsed disease (n=11). The overall response rate for low grade lymphoma was 88% (63% complete remission) in untreated patients and 79% (43% complete remission) in those with relapsed disease. Common adverse events were myelosuppression and infection. Two patients died of sepsis and 4 due to disease progression on treatment. Median event-free survival for patients treated upfront with fludarabine was 31.4 months. CONCLUSION: In our patient population, response to fludarabine is similar to that in the published literature. Our patients had a higher frequency of haematological toxicity.

Cytomegalovirus oesophagitis in a patient with Non-Hodgkin's lymphoma.

Cytomegalovirus (CMV) infection is frequent in immunocompromised patients, especially in AIDS, organ transplantation and rarely in Hodgkin's disease and Non-Hodgkin's lymphoma (NHL). We present a case of NHL with CMV oesophagitis, which has rarely been documented in literature. Apart from fungal and herpes simplex infections, as the common differential diagnosis for oesophagitis in patients of lymphoma, CMV should be considered an important etiologic agent. Early diagnosis and prompt treatment of CMV oesophagitis with gancyclovir can avert significant morbidity and avoid unacceptable treatment delays.

Successful complete regression of isolated intramedullary spinal cord metastases from epithelial ovarian carcinoma with chemotherapy and radiotherapy.

Advances in the management of ovarian cancer by use of aggressive surgery and effective platinum-based chemotherapy have prolonged survival; this may have resulted in an alteration of the metastatic pattern of the disease and spread to unusual sites (e.g, CNS) has become more common. Also, with the availability of more sensitive imaging techniques, these tumors are being diagnosed with increasing frequency. Intramedullary spinal cord metastasis is rare. We report one such case treated successfully with chemotherapy and radiotherapy with long-term survival.

Rituximab (anti-CD20 monoclonal antibody) in lymphoproliferative malignancies: Tata Memorial experience.

Rituximab has been used extensively in lymphoproliferative disorders. We evaluated the results of 64 consecutive patients treated between 2001 and 2004 at our institution. This included 54 males and 10 females. The median age was 54 years (range 17 to 85 years). One-fourth of patients were above 60 years. The histology was aggressive NHL in 35, indolent NHL in 22 and 7 cases were diagnosed as CLL. Among NHL, sixteen were in early stage (I/II) and the remaining forty-one were in advanced stage (III/IV) of disease. B symptoms were present in 47% of cases. A total of 33 were de novo cases and 31 were previously treated. Rituximab monotherapy was used in 17 cases. Rituximab was used in combination with chemotherapy in the other 47 cases. Infusional toxicity included anaphylaxis in one, hypotension in one and minor infusional reactions in four others. The patient who developed anaphylaxis required discontinuation of further Rituximab. Growth factors were used in 25 patients. Febrile neutropenia occurred in 19 patients. The overall RR (CR + PR) was 72%. One patient had stable disease and progressive disease was documented in 17 patients. A total of seven patients died, three due to progressive disease, three due to chemotherapy related toxicity and one due to an unrelated cause. We conclude that Rituximab is a valuable addition to the treatment armamentarium of lymphoproliferative disorders.

Ewing's sarcoma with cutaneous metastasis--a rare entity: report of three cases.

Ewing's sarcoma (ES) is a small round cell tumor, usually arising from flat bones and diaphyseal region of long bones. It is commonly found in the first two decades of life. It is curable when diagnosed in the localized stage and requires multimodality treatment. ES is a chemosensitive tumor. It metastasizes commonly to lung, pleura and other bones. Less common sites of metastasis are lymph nodes, CNS and liver. Skin metastasis is extremely uncommon. It occurs in up to 9% of all patients with cancer. Growth pattern of cutaneous metastasis is unpredictable and may not reflect that of primary tumor. We hereby report three cases of Ewing's sarcoma that developed skin metastasis.

Imatinib mesylate in chronic myeloid leukemia: a prospective, single arm, non-randomized study.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder characterized by the balanced reciprocal translocation t (9:22). The resulting fusion gene, the BCR-ABL, is responsible for oncogenesis. Imatinib mesylate is a novel molecule, which inhibits the protein product of this fusion gene and hence has been used in the treatment of CML. The present study evaluates 174 patients with CML treated with imatinib mesylate. Of these 174 patients, 97 were in chronic phase, 47 in accelerated phase and 30 patients had blast crisis. Patients in chronic phase received imatinib mesylate in the dose of 400-mg daily, while those in accelerated phase and blast crisis received 600 to 800 mg daily. Of the 97 patients with chronic phase, 49 patients (50.5%) achieved a major (major + complete) cytogenetic response. Of the 47 patients in accelerated phase, 10 patients (21.3%) achieved a major cytogenetic response and in 30 patients with blast crisis, 7 (23.3%) achieved a major cytogenetic response. Dermatitis, mucositis, neutropenia and thrombocytopenia were some of the major toxicities. Of interest, 121 of the 174 patients (69.5%) developed generalized hypopigmentation. We conclude that imatinib mesylate is a safe and effective first-line therapy for chronic myeloid leukemia.

Yolk sac tumor of vagina.

Yolk sac tumors are common in children. By virtue of being chemosensitive, they are amenable to cure by chemotherapy alone and radical surgery is often not required. Yolk sac tumors occurring in the vagina are rare and thus may not be recognized early or may be inadvertently subjected to radical surgery. The authors report a case that presented to them after radical surgery with elevated Alpha-fetoprotein level is reported. The management of this case and review of the relevant literature are discussed here.

Outcome of acute myeloid leukaemia in adults: a retrospective analysis.

BACKGROUND: There are little data from India on the management of acute myeloid leukaemia. With better understanding of the biology of the disease, and routine use of high-dose cytarabine as post-remission therapy with or without haematopoietic blood stem cell transplantation (HSCT), the results have improved in the past two decades. We analysed our results in a cohort of recently treated patients. METHODS: A total of 166 newly diagnosed patients with AML (excluding acute promyelocytic leukaemia), 15-60 years of age were treated with daunorubicin (60 mg/m2/day x3 days) or idarubicin (12 mg/m2/day x3 days) with cytarabine (100 mg/m2/day continuous i.v. infusion x7 days) induction chemotherapy. Post-remission therapy included 2 cycles of high-dose cytarabine (15-18 g/m2) followed by monthly cycles of outpatient maintenance chemotherapy x4 cycles, consisting of daunorubicin (45 mg/m2 i.v. x1 day and cytarabine 100 mg/ m2 s.c. twice daily x5 days). Six patients in remission received sibling donor allogeneic HSCT. RESULTS: Morphological complete remission was achieved in 69.9% of the patients. Resistant disease after induction chemotherapy was seen in 14.6% and early mortality occurred in 16%. Relapse-free survival and event-free survival at a median of 36 months was 34% and 22%, respectively. Relapse occurred in 43.9%. The median duration of remission was 12 months. CONCLUSIONS: Our results conform to the published literature from larger cooperative studies from the West. Currently available cytotoxic drugs are unlikely to improve the results any further.

Basilar artery vasospasm after severe head injury: a preliminary transcranial Doppler ultrasound study.

BACKGROUND: Post-traumatic vasospasm after severe head injury is now a well known entity. However, all studies available in the literature have evaluated only the anterior cerebral circulation. We evaluated the incidence of basilar artery vasospasm in patients with severe head injury. METHODS: Basilar artery mean blood flow velocity was measured in 16 patients with severe closed head injury (Glasgow Coma Scale 8 or less) using transcranial Doppler ultrasonography. Ten normal subjects also underwent the same investigation. The patients' age ranged from 5 to 65 years. The study group included 13 males and 3 females. All patients underwent serial CT scans. In 10 patients the blood flow velocity was measured within 72 hours of the injury and in the remaining 6 it was done within 4 days to 3 weeks after the injury. RESULTS: The basilar artery could be insonated easily in all the patients. The depth of insonation ranged from 65-85 mm in adults and 50-60 mm in children (n = 2). The mean blood flow velocity in severely head-injured patients was 47.4 cm/second which was significantly higher than the normal value of 42 cm/second (p < 0.008). Eight of the 14 adults (57%) had a mean blood flow velocity higher than the control value. In 7 (50%) of these the velocity was higher than 60 cm/second. Seven of these 8 patients with a high blood flow velocity had evidence of diffuse brain injury on CT scan. Six of them had effacement of the basal cisterns as a result of diffuse brain oedema. Among the remaining 8 patients who had contusion and haematoma on CT scan, only 2 had a high blood flow velocity in the basilar artery. CONCLUSION: Basilar artery blood flow velocity is higher in patients with severe head injury. Patients with diffuse brain injury have a particularly high velocity. Thus, it may be an easy method to assess the severity of head injury. The temporal profile of basilar artery vasospasm needs to be established in severely head-injured patients to assess its clinical utility.