Mauricette Michallet

Response to imatinib in patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia

We studied 128 patients with chronic myeloid leukemia (CML) relapsing after allogeneic stem cell transplantation (SCT). Disease at the time of treatment with Imatinib was in chronic phase (CP) in 51 patients, accelerated phase (AP) in 31 and blastic crisis (BC) in 46. Of the 51 patients in CP, 14 were in cytogenetic and two in molecular relapses. The median interval between relapse and Imatinib therapy was 5 months (0–65). A total of 50 patients had failed treatment with donor lymphocyte infusions prior to Imatinib. The overall hemato-logical response rate was 84% (98% for patients relapsing in CP). The complete cytogenetic response (CCR) was 58% for patients in CP, 48% for AP and 22% for patients in BC. Complete molecular responses were obtained in 25 patients (26%), of whom 21 were in CP or AP. With a median follow-up of 9 months, the estimated 2-year survival for CP, AP and BC patients was 100, 86 and 12%, respectively. Out of 79 evaluable patients, 45 (57%) achieved full donor and 11 (14%) mixed chimerism after Imatinib. We conclude that Imatinib has significant activity against CML in relapse after allogeneic SCT. Durable cytogenetic and molecular remissions are obtainable in patients in CP.

Allogeneic bone marrow transplantation in aggressive non-Hodgkin's lymphoma (excluding Burkitt and lymphoblastic lymphoma): a series of 73 patients from the SFGM database

The place of allogeneic bone marrow transplantation (BMT) in the treatment of aggressive non‐Hodgkins lymphoma (NHL) remains controversial. We conducted a retrospective study of French experience in allografting NHL between 1984 and 1994. To improve the homogeneity of the study population, cases of low‐grade, Burkitt and lymphoblastic NHL were excluded. 73 patients were included in the analysis. Median age at transplantation was 35 years (range 9–61 years); 64 patients were in stage IV and 45 had bone marrow involvement at diagnosis. At the time of transplantation, 46 patients had sensitive disease (25 in complete remission; CR).

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10−7). We identified a subgroup of patients presenting at diagnosis with both low β2-microglobulin <4u2009mg/l and high hemoglobin (Hb) ⩾10u2009g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high β2-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.

BCR-ABL T315I transcript disappearance in an imatinib-resistant CML patient treated with homoharringtonine: a new therapeutic challenge?

BCR-ABL T315I transcript disappearance in an imatinib-resistant CML patient treated with homoharringtonine: a new therapeutic challenge?

Stem cell collection in patients with de novo multiple myeloma treated with the combination of bortezomib and dexamethasone before autologous stem cell transplantation according to IFM 2005-01 trial

Stem cell collection in patients with de novo multiple myeloma treated with the combination of bortezomib and dexamethasone before autologous stem cell transplantation according to IFM 2005–01 trial

Prior treatment with alpha interferon does not adversely affect the outcome of allogeneic transplantation for chronic myeloid leukaemia

Summary. The timing of transplantation in chronic myeloid leukaemia is still debated and previous treatment with interferon (IFN) alpha has been reported to be deleterious. We have analysed the outcome of 438 allogeneic transplants performed between 1984 and 1995 and reported to the Société Française de Greffe de Moelle (SFGM) registry. One hundred and two patients (group I) received IFN for more than 6u2003weeks (median =u200a9u2003months) before transplant. Their outcome was compared with 336 other patients (group II) not pretreated with IFN. There were no significant differences between the groups for engraftment and chronic graft‐versus‐host disease (GVHD) incidence. However, other significant differences included the incidence of acute GVHD ≥u200a2 at 3u2003months which was higher in group I (65u2003±u200310%) than in group II (38u2003±u20035%; Pu2003=u20030·01). Moreover, disease‐free survival (DFS) and overall survival (OS) at 5u2003years were significantly shorter for group I than for group II (33u2003±u200310% vs. 41u2003±u20036%; Pu2003=u20030·005)(95% CI) and (41u2003±u200310% vs. 55u2003±u20036%; Pu2003=u20030·002)(95% CI) respectively. After adjustment for patient and transplant covariables in a multivariate analysis, prior IFN was not found to adversely affect transplant outcome.

Identification of a rare e6a2 BCR-ABL fusion gene during the disease progression of chronic myelomonocytic leukemia: a case report

Identification of a rare e6a2 BCR-ABL fusion gene during the disease progression of chronic myelomonocytic leukemia: a case report

The post-transplant cytogenetic response to interferon is a major determinant of survival after autologous stem cell transplantation for chronic myeloid leukaemia in chronic phase

Summary. We have analysed the outcome of 581 autologous stem cell transplants (SCT) for chronic myeloid leukaemia (CML) in first chronic phase reported to the European Group for Blood and Marrow Transplantation between 1983 and 1998. Out off 207 patients evaluable for cytogenetics within 6u2003months of SCT, 36 patients (17%) were in complete cytogenetic remission (CCR), 34 (16%) in major remission (MCR), 74 (36%) in minor remission (mCR) and 63 (31%) had no cytogenetic response (NR). Interferon (IFN) was given post SCT to 267 patients. Results of the cytogenetic analysis within 1–2u2003years from SCT were available for 117 patients, the majority of whom (nu2003=u2003101) received IFN post SCT: 17 (15%) were in CCR, 18 (15%) in MCR, 24 (20%) in mCR and 58 (50%) NR. The median survival in this series was 96u2003months (71–125) from SCT. There was no difference in survival according to cytogenetic status pre‐ and immediately post SCT. However, patients in CCR or MCR at 1–2u2003years post SCT had a 10‐year survival of 66% compared with 36% for patients in mCR or NR (Pu2003=u20030·003). The 5‐year survival for patients receiving IFN post SCT was 72% compared with 61% for patients not treated with IFN (Pu2003=u20030·01). Out of 155 patients refractory to IFN pre SCT, 70% achieved a cytogenetic response post SCT, which was complete or major in 31%. IFN refractory patients who sustained a CCR or MCR for 1–2u2003years after SCT had an excellent outcome.

Heavy+light chain monitoring correlates with clinical outcome in multiple myeloma patients

Novel anti-myeloma agents have improved patient response rates, which are historically based on reductions of the M-protein. These methods can be inaccurate for quantifying M-proteins at low concentrations. We compared the consistency and clinical impact of response assignment by electrophoretic and heavy+light chain (HLC) immunoassays post-consolidation in 463 newly diagnosed patients. The two methods gave similar assignments in patients with partial (PR; 79% agreement) or complete response (⩾CR; 92%). However, in patients achieving very good PR (VGPR) there was poor concordance between methods (45%). Median progression-free survival (PFS) for standard VGPR patients was 34.5 months; HLC responses stratified these patients further into PR, VGPR and ⩾CR, with median PFS of 21.3, 28.9 months and not reached, respectively; P<0.001. At this time, abnormal HLC ratios had better concordance with multiparametric flow cytometry (sensitivity 10−4) (37 and 34% positive, respectively), compared to immunofixation (62% positive). In addition, HLC-pair suppression was identified in 38% of patients and associated with shorter PFS (30.6 months vs not reached; P<0.001). We conclude that HLC monitoring could augment electrophoretic assessments in patients achieving VGPR. The prognostic significance of HLC responses might partly depend on the patients’ ability to recover their immune system, as determined by normalisation of HLC measurements.

How to prevent relapse after allogeneic hematopoietic stem cell transplantation in patients with acute leukemia and myelodysplastic syndrome

Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT). The risk of recurrence is elevated in acute myeloid leukemia (AML) patients with high-risk cytogenetic or molecular abnormalities, as well as when allo-HCT is performed in patients with refractory hematological malignancies or with persistent molecular or radiological (PET-CT scan) residual disease. For high risk AML and myelodysplasia (MDS), a post transplant maintenance strategy is possible, using hypomethylating agents or tyrosine kinase inhibitors (TKI) anti-FLT3 when the target is present. For Philadelphia positive acute lymphoblastic leukemia (ALL), there is a consensus for the use of TKI anti BCR-ABL as post transplant maintenance.