Outcome of myeloablative conditioning and unrelated donor hematopoietic cell transplantation for childhood acute lymphoblastic leukemia in third remission.

We conducted a retrospective study of 155 children who underwent unrelated donor hematopoietic cell transplantation (HCT) between 1990 and 2005 for acute lymphoblastic leukemia in third remission. The median patient age was 11 years, the median time from diagnosis to first relapse was 36 months, and the median time from first relapse to second relapse was 26 months. Stem cell sources were bone marrow (n = 115), peripheral blood (n = 11), and cord blood (n = 29). All patients received a myeloablative pretransplantation conditioning regimen. The 5-year estimates of leukemia-free survival, relapse, and nonrelapse mortality were 30%, 25%, and 45%, respectively. In multivariate analysis, the only risk factor associated with relapse was the interval between the first relapse and the second relapse. Second relapses occurring >26 months from the first relapse were associated with lower risk for post-HCT relapse compared with second relapses occurring at ≤26 months (relative risk, 0.4; P = .01). Relapse risk was lowest when late second relapse was preceded by late first relapse (>36 months from diagnosis), as demonstrated by a 3-year relapse rate of 9% (P = .0009). Our data indicate that long-term leukemia-free survival can be achieved in children with acute lymphoblastic leukemia in third remission using unrelated donor HCT, especially when the second relapse occurs late.

Effects of thyroid hormone analogue and a leukotrienes pathway-blocker on renal ischemia/reperfusion injury in mice.

BACKGROUND: Acute renal failure (ARF) is an important clinical problem with a high mortality and morbidity. One of the primary causes of ARF is ischemia/reperfusion (I/R). Inflammatory process and oxidative stress are thought to be the major mechanisms causing I/R. MK-886 is a potent inhibitor of leukotrienes biosynthesis which may have anti-inflammatory and antioxidant effects through inhibition of polymorphonuclear leukocytes (PMNs) infiltration into renal tissues. 3, 5-diiodothyropropionic acid (DITPA) have evidences of improving effects on I/R in heart through modulation of cellular signaling in response to ischemic stress. The objective of present study was to assess the effects of MK-886 and DITPA on renal I/R injury. METHODS: A total of 24 Adult males of Swiss albino mice were randomized to four groups: I/R group (n = 6), mice underwent 30 minute bilateral renal ischemia and 48 hr reperfusion. Sham group (n = 6), mice underwent same anesthetic and surgical procedures except for ischemia induction. MK-886-treated group: (n = 6), I/R + MK-886 (6 mg/kg) by intraperitoneal injection. DITPA-treated group: (n = 6), I/R + DITPA (3.75 mg/kg) by intraperitoneal injection.After the end of reperfusion phase mice were sacrificed, blood samples were collected directly from the heart for determination of serum TNF-a, IL-6, urea and Creatinine. Both kidney were excised, the right one homogenized for oxidative stress parameters (MDA and GSH) measurements and the left kidney fixed in formalin for histological examination. RESULTS: Serum TNF-α, IL-6, urea and Creatinine, kidney MDA levels and scores of histopathological changes were significantly (P < 0.05) elevated in I/R group as compared with that of sham group. Kidney GSH level was significantly (P < 0.05) decreased in I/R group as compared with that of sham group. MK-886 treated group has significantly (P < 0.05) lowered levels of all study parameters except for GSH level which was significantly (P < 0.05) higher as compared with that of I/R group. DITPA caused non-significant (P > 0.05) changes in levels of all study parameters as compared with that of I/R group. CONCLUSION: The results of the present study show that MK-886 significantly ameliorated kidney damage that resulted from I/R. For DITPA, as its administration might not be successful, administration using a different protocol may give different effects on I/R.