Continued from page 10


Despite the success of UCBT in children, this strategy does not work as well for adults due to low cell doses and mismatches. A new strategy of using a double UCB platform seems to markedly increase the eligibility of adults for UCBT and appears to positively impact survival. Additionally, nonmyeloablative therapy clearly extends the eligibility with a low incidence of transplant-related mortality. Finally, a new approach that is being developed is to reduce nonspecific SC losses and optimize homing by direct injection into the pelvis (the BM microenvironment).


In conclusion, allogeneic SCT is a viable option for patients without an exact match. Alternatively, recent data have shown that unmatched CB has greater success than either BM or PBSCs that are unmatched. Furthermore, UCBT is the standard of care in children, but the double UCB platform and nonmyeloablative therapy have markedly extended the use of UCBs in adults. It seems that interest in UCB will not wane in the near future as more benefits and applications are being realized.


Continued from page 31


only 54%, according to Dr. DeMatteo’s earlier research (Ann Surg 2000). DeMatteo and colleagues hypothesized that adjuvant imatinib would prolong RFS following the complete resection of primary GIST.


The main entry criterion was primary GIST size of ≥3 cm. All patients had complete gross resection of KIT+ tumors and were randomized to a year of either placebo or 400 mg daily of imatinib. The endpoints were recurrence-free survival (RFS, primary), overall survival (OS, secondary), and safety. Progressing patients were unblinded and switched from placebo to imatinib 400 mg or from imatinib 400 mg to 800 mg/day.


After the third scheduled 6-month analysis, with 644 of a planned 732 patients enrolled, the trial was stopped prematurely. Similar percentages of the prescribed dose were delivered to both groups (placebo 71%, imatinib 67%), with tumor recurrence (38% placebo, 1% imatinib) and toxicity (7% placebo, 50% imatinib) the main causes, respectively, of dose alterations. Grade 3-4 toxicities with imatinib were mainly neutropenia, liver function test elevations, skin rash, and edema.


OS was similar in both groups, with a surprisingly small number of events (4 deaths placebo, 3 deaths imatinib, p=0.72), Dr. DeMatteo said. Six were attributed to


Photo Courtesy © ASCO/Todd Buchanan 2007


disease recurrence. For the primary PFS endpoint at 1year, there were 62 events in the placebo arm and 21 in the imatinib arm (83% vs 97%, p=0.001). Dr. DeMatteo pointed out that at about 6 months after the completion of treatment, the RFS slope began to turn downward.


Subgroup analysis showed stronger imatinib effects in patients with the largest tumors (≥10 cm), with RFS of 67% in the placebo arm and 96% in the imatinib arm (p=0.001), and a descending PFS slope at about 1.5 years.


Dr. DeMatteo concluded, “One year of 400 mg/day imatinib mesylate is safe and well tolerated after the complete resection of a primary gastrointestinal stromal tumor. Recurrence-free survival is increased. Overall survival has not been altered at this time with these preliminary data.”


Continued from page 33


There were 3 toxic deaths in Head Start I and 1 in Head Start II. Five patients relapsed in Head Start I, whereas only two patients did so in Head Start II; all relapses developed within 25 months and the majority occurred locally. Overall quality of life (QoL) was within the average range at both times of assessment (70 months and 124 months); younger patients displayed fewer behavioral problems and higher adaptive function at both time points.


In conclusion, EFS in this study mirrors that reported in the German HIT study [Rutkowski et al. New Eng J Med 2005]. Incomplete resection and absence of desmoplasia trend toward inferior EFS, but not OS. These results show that, despite administering the myeloablative chemotherapy, these patients can be retrieved with either more chemotherapy or irradiation. Although the number of patients is limited in these studies, the QoL was within the normal range in the Head Start I study, and it was improved in three of four patients in the Head Start II study.


30


August 2007


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30