The tyrosine kinase inhibitor STI571 (imatinib mesylate, Gleevec) is an effective treatment for chronic myeloid leukemia (CML). We examined bone marrow samples from 53 patients with CML who were receiving STI571 in 3 multicenter phase 2 trials to assess morphologic changes and cytogenetic response to this drug. In most patients with initially increased blasts, the bone marrow blast count rapidly decreased during STI571 therapy. Reductions in cellularity, the myeloid/erythroid ratio (commonly with relative erythroid hyperplasia), and reticulin fibrosis (if present pretreatment) also were seen in most patients, resulting in an appearance resembling normal marrow in many cases. Eighteen patients (34%) had some degree of cytogenetic response. Surprisingly, these striking morphologic changes occurred irrespective of any cytogenetic response to STI571. Thus, STI571 seems to affect the differentiation of CML cells in vivo, causing even extensively Philadelphia chromosome-positive hematopoiesis to exhibitfeatures resembling normal hematopoiesis.

The immunologic features of leukemic cells at the time of 1stondary acute myeloid leukemias (AML) has been described in hematologic relapse were compared to those obtained at initial children previously treated for ALL with regimens containing diagnosis in 128 patients (69 children and 59 adults) with acute teniposide on a twice weekly schedule. 8,9 It is, therefore, use- med in all children and adults with ALL in 1st relapse at ourIn 21 cases, the immunophenotype at relapse was more undifferentiated than at diagnosis, while it was more differentiated Institution and compared to the phenotype observed at diag- from 0.1 to 85 years. The diagnosis of ALL was based on FAB Keywords: immunophenotype; lymphoblastic; leukemia; relapse criteria 10 and immunophenotype. [11][12][13] Response to treatment was evaluable in 482 patients. The 32 unevaluable cases included 18 referred only for diagnosis and 14 that were Introduction treated only with palliative therapy. 443 patients achieved a complete remission (CR) (92%) and 209 of these subsequently Relapses of acute lymphoblastic leukemia (ALL) occur with relapsed. A comparison between the immunophenotypic prodifferent frequencies according to patients' age, being higher files at relapse and at diagnosis was not carried out in 14 in infants and adults compared to children. Several studies patients who presented at relapse with Ͻ30% blasts in the have focused on the immunophenotype of the leukemic popubone marrow aspirate and in 67 patients because of an incomlation at the time of relapse compared to that observed at diagplete immunophenotype performed at the time of presentation nosis. [1][2][3][4][5][6][7] Although in the majority of cases a modification in and/or at 1st relapse. A total of 128 patients were evaluable, the phenotypic profile of the neoplastic clone does not occur, including 69 children (median age 7 years, 0.2-14.8) and 59 in a notable number of B and T lineage ALL immunophenoadults (median age 30.8 years, 15-67). Median duration of 1st typic changes have been recorded. In most cases, these are CR was 16 months (range 2-80), shorter than 1 year in 51 represented by a loss of differentiation antigens, suggesting patients and longer in 77. All patients were treated at diagthat relapses may originate from a more undifferentiated subnosis and at relapse with anti-ALL chemotherapy regimens in clone of leukemic blasts. In childhood ALL, an overall change order to achieve CR and long-term event-free survival (EFS). in the immunophenotype at relapse does not seem to influSince over the years different treatment protocols were ence the response to salvage therapy, but relapses of T lineage employed these have been grouped under two major categor-ALL have been associated with a worse outcome compared ies: standard and intensive. Standard treatment schemes to B lineage ALL. 5 included a four drug induction (anthracycline, vincristine, L-A phenotypic change at relapse does not necessarily imply asparaginase, prednisone), followed by consolidation, reinthat a new l...

We conclude that in contrast to normal cell engraftment, engraftment of CML cells in NOD/SCID mice is characterized by a slow but progressive myeloid infiltration, which eventually consists almost entirely of mast cells.

Summary:In the last 3 years, 14 children with high-risk leukemia (11 ALL, 2 AML and 1 CML) underwent cord blood transplantation from unrelated HLA-mismatched donors at a median of 99 days from the start of search. Eight patients were transplanted in second CR, one in accelerated phase, three at relapse and two patients in first CR. Conditioning regimen (fractionated TBI, etoposide, CY and anti-lymphocyte serum) and prophylaxis of GVHD (CsA and 6-methylprednisolone) were identical for all patients. Neutrophils > 0.5 ؋ 10 9 /l were reached at a median of 33 days from transplant, but in four cases we observed an autologous hematopoietic reconstitution (three spontaneous, one after autologous BM rescue). Acute and chronic GVHD were observed in 10/14 and 3/8 evaluable cases, respectively. Three patients died of transplant-related toxicity and three patients relapsed. The probabilities of event-free, disease-free and overall survival were 50, 53 and 64%, respectively. Cord blood transplant from HLA-mismatched unrelated donor is a valid option for the treatment of children with high-risk leukemia. With our eligibility criteria, conditioning regimen and prophylaxis of graft-versus-host disease, the main obstacles to successful transplant were represented by graft failure and fatal acute GVHD. Keywords: cord blood; leukemia; children; transplantation The majority of children and a significant proportion of adults with acute leukemia may be cured of their disease by standard treatments which do not include up-front allogeneic BMT. However, some patient categories are predicted to have a dismal outcome and may be salvaged by supralethal chemoradiotherapy followed by allogeneic BM rescue. Alternative sources of hemopoietic stem cells might be exploited in patients lacking an HLA-matched related or unrelated BM donor.Hemopoietic progenitor cells have been recognized in the umbilical cord blood (UCB) since 1974. 1 Thereafter, Correspondence: Dr W Arcese, Cattedra di Ematologia, via Benevento 6, 00161 Roma, Italy Received 11 September 1998; accepted 29 October 1998 many studies suggested that the UCB could be employed for transplantation, 2 and finally the first UCB transplant was successfully performed in a patient with Fanconi anemia in 1988. 3 The indication for a UCB transplant extended rapidly from patients with an HLA-matched or -mismatched sibling donor 4 to candidates for transplantation from unrelated donors. [5][6][7] As an alternative to international bone marrow donor registries, the expansion of UCB banks both in Europe and in North America opened new perspectives of transplantation for a significant proportion of leukemic patients lacking an HLA-matched related donor. [8][9][10] Therefore since April 1995 we adopted a policy of searching stem cell sources in UCB banks for patients with high risk leukemia. So far, 14 patients prepared with an identical regimen of conditioning and GVHD prophylaxis have been submitted to an HLA-mismatched unrelated UCB transplant. Five of these patients (UPN 300, UPN 312, UPN 324, U...