Limited information is available from developing countries about complications, pattern of infections, and long-term outcome of patients following high-dose chemotherapy (HDCT) and autologous blood stem cell transplantation (ASCT). Between April, 1990 and December 2009, 228 patients underwent ASCT. Patients' median age was 48 years, ranging from 11 to 68 years. There were 158 males and 70 females. Indications for transplant included multiple myeloma, n = 143; lymphoma, n = 44 (Hodgkin's, n = 25 and non-Hodgkin's, n = 19); leukemia, n = 22; and solid tumors, n = 18. Patients received HDCT as per standard protocols. Following ASCT, 175 (76.7%) patients responded; complete, 98 (43%); very good partial response, 37 (16.2%); and partial response, 40 (17.5%). Response rate was higher for patients with good Eastern Cooperative Oncology Group (ECOG) performance status (0-2 vs. 3-4, p < 0.001), pretransplant chemo-sensitive disease (p < 0.001) and those with diagnosis of hematological malignancies (p < 0.003). Mucositis, gastrointestinal, renal, and liver dysfunctions were major nonhematologic toxicities, 3.1% of patients died of regimen-related toxicities. Infections accounted for 5.3% of deaths seen before day 30. At a median follow-up of 66 months (range, 9-234 months), median overall (OS) and event-free survival (EFS) were 72 months (95% CI 52.4-91.6) and 24 months (95% CI 17.15-30.9), respectively. For myeloma, OS and EFS were 79 months (95% CI 52.3-105.7) and 30 months (95% CI 22.6-37.4), respectively. Pretransplant good performance status and achievement of significant response following transplant were major predictors of survival. Our analysis demonstrates that such procedure can be successfully performed in a developing country with results comparable to developed countries.
To the Editor: Leucovorin is used as rescue agent after high dose methotrexate or to enhance efficacy of 5-Flurouracil. A 16-year-old male with Stage III T cell lymphoblastic lymphoma achieved complete remission following induction on BFM-90 protocol [1]. He received first course of high dose methotrexate 5 g/m 2 with leucovorin rescue which was uneventful. Following the second dose of high dose methotrexate, he was given leucovorin intravenously at doses of 30 mg/m 2 at hour 42 and 15 mg/m 2 each at hours 48 and 54. There was no reaction with first dose of leucovorin. Immediately after second dose, patient developed chills and rigors, followed by erythematous rash over face, neck and upper limbs along with a temperature spike of 38.88C; the patient responded to antihistaminics. Following the third dose of leucovorin, there was a generalized erythematous rash that blanched on pressure; the patient also had vomiting, dizziness and hypotension but no bronchospasm. Dopamine, anti-histaminics and hydrocortisone were started. The erythematous rash subsided over 24 hr but hypotension persisted for 42 hr. His serum creatinine increased from 0.9 mg/dl at baseline to 1.5 mg/dl on day 4. Hydration and alkalinization were continued following which serum creatinine levels returned to normal on day 7 from the start of methotrexate infusion.In view of a single febrile episode after second dose and hypotension, the possibility of sepsis was considered and intravenous antibiotics were administered. Blood culture and chest radiograph were normal. Serum procalcitonin level, a marker of sepsis [2], was 2.1 ng/ml (<0.5: localized infection, !0.5-2: possible systemic infection; !2-10: systemic infection likely unless other causes are known; !10: exclusively due to severe sepsis). Serum IgE levels were 711 IU/ml (normal: 0.0-158 IU/ml). Thus, a final diagnosis of systemic reaction to leucovorin suggestive of hypersensitivity was made. Further chemotherapy was continued as per protocol but all high doses of methotrexate requiring leucovorin rescue were omitted.Hypersensitivity reactions to leucovorin have been previously reported in patients receiving treatment for colorectal cancer [3,4]. Our patient received high dose methotrexate with ondansetron 48 hr before the occurrence of adverse reaction and no other concomitant medications were in use except intravenous fluids. The presence of near normal procalcitonin level, sterile blood culture and absence of any focus of infection ruled out sepsis as a cause of the above episode. Typically hypotension in anaphylaxis is of short duration although it may be occasionally prolonged [5]. Allergy to folic acid is well known with presence of elevated folate specific antibodies [6,7]; however, leucovorin hypersensitivity is rare. Our report emphasizes that leucovorin hypersensitivity can be observed in children and provides awareness of this possible serious reaction to an otherwise innocuous antidote.
Spinal primitive neuroectodermal tumor (PNET) is rare. We present clinical, radiologic profile and treatment outcome of 15 spinal PNET patients from June 2003 to March 2010 treated with chemoradiotherapy. Median duration of backache was 6.5 months; all had features of myelopathy and/or radiculopathy; 5/15 (33.3%) patients were diagnosed initially as spinal tuberculosis. The event-free survival (EFS) was 24.73% at a median follow-up of 22 months. Complete functional recovery to treatment significantly predicted better EFS; 4 patients discontinued treatment because of poor functional recovery. It is important to recognize spinal PNET early to prevent permanent neurological damage, which in turn would improve compliance, quality of life, and perhaps EFS.
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