Imatinib Mesylate Treatment of Patients with Chronic Myeloid Leukaemia Relapsing Following Allogeneic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4659-4659
Author(s):  
Eibhlin Conneally ◽  
Peig Carroll ◽  
Michael Neat ◽  
Karl Haslam ◽  
Kathy Gately ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Chronic Myeloid Leukaemia ◽  
Disease Free Survival ◽  
Molecular Remission ◽  
Bone Marrow Aplasia ◽  
Free Survival ◽  
Disease Free

Abstract Stem Cell Transplantation (SCT) is associated with long-term disease-free survival in patients transplanted for Chronic Myeloid Leukaemia (CML). However a proportion of patients continue to have haematological, cytogenetic or molecular relapses up to fifteen years following SCT. Donor lymphocyte infusions (DLI) given post SCT relapse are associated with long-term molecular remissions and disease-free survival but depend on the availability of the original donor. In addition the use of DLI can be complicated by both Graft vs Host Disease (GvHD) and bone marrow aplasia. We have treated 10 patients (pts) who relapsed following SCT with imatinib mesylate (IM). 4/10 pts had previously received DLI for haematological relapse. The propositus was unable to receive DLI because his donor had died, hence the initial impetus for the study. IM was given at a dose of 300mg–600mg/day and was well tolerated in all patients. All pts were evaluable for a response to IM. Response to the treatment was evaluated by bone marrow analysis, karyotypic and molecular analysis. Molecular analysis for BCR-ABL was performed by nested RT-PCR and by real time RQ-PCR using TaqMan probes for BCR-ABL and ABL transcripts in serial samples following treatment with IM. 59 samples from the 10 pts (median 4, range 2–13) were analysed by PCR analysis. Time points ranged from 1–38 months post commencement of IM therapy (median 11 months). The cohort was comprised of 7 males and 3 females. Median age: 33 years (26–48 years). 9 pts received bone marrow as the source of stem cells, 1 pt received peripheral blood stem cells: 8 pts from a histo-compatible sibling donor, 1 unrelated donor, and 1 related phenotypically identical donor. Median time to first relapse was 32 months (range 7 months–120 months). 5 pts were treated with IM at the time of haematological relapse (n=3) or cytogenetic relapse (n=2). 3/5 responded with both a cytogenetic and molecular remission (BCR-ABL transcripts <10−5) achieved by 21, 36, 36 months post IM therapy. 1 pt treated for cytogenetic relapse has falling BCR-ABL transcripts 6 months post initiation of treatment. The other pt was treated in accelerated phase (AP), failed to respond and died. The remaining 5 pts were treated following molecular relapse. Although the follow-up is shorter than in the first group, 4/5 pts have shown evidence of molecular remission at 3, 3, 3, 4 months post IM therapy. One patient transplanted in AP had progressive disease. No patient experienced GvHD following IM treatment. 8/10 pts are alive and receiving IM 3–13 years following their original SCT. In conclusion, IM induces durable clinical, cytogenetic and molecular responses in patients treated for relapse of CML post SCT without the side effects of GvHD and bone marrow aplasia. The kinetics of minimal disease conversion indicates a more rapid response in patients treated in molecular relapse. A comparison of DLI versus IM in patients relapsing more than one year after transplant should be undertaken.

Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in first remission: a cooperative study of the Groupe d'Etude de la Greffe de Moelle Osseuse.

1989 ◽  
Vol 7 (6) ◽  
pp. 747-753 ◽  
Author(s):  
P Bordigoni ◽  
J P Vernant ◽  
G Souillet ◽  
E Gluckman ◽  
D Marininchi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Allogeneic Bone ◽  
Free Survival ◽  
Disease Free

Thirty-two children ranging in age from 1.5 to 16 years with poor-prognosis acute lymphoblastic leukemia (ALL) were treated with myeloablative immunosuppressive therapy consisting of cyclophosphamide (CPM) and total body irradiation (TBI) followed by allogeneic bone marrow transplantation (BMT) while in first complete remission (CR). The main reasons for assignment to BMT were WBC count greater than 100,000/microL, structural chromosomal abnormalities, and resistance to initial induction therapy. All children were transplanted with marrow from histocompatible siblings. Twenty-seven patients are alive in first CR for 7 to 82 months post-transplantation (median, 30 months). The actuarial disease-free survival rate is 84.4% (confidence interval, 7.2% to 29%) and the actuarial relapse rate is 3.5% (confidence interval, 0.9% to 13%). Four patients died of transplant-related complications, 16 developed low-grade acute graft-v-host disease (GVHD), and six developed chronic GVHD. The very low incidence of relapse (one of 28 long-term survivors) precluded the determination of the prognostic significance of the different poor-outcome features. Moreover, two infants treated with busulfan, CPM, and cytarabine (Ara-C) relapsed promptly in the marrow. In summary, as a means of providing long-term disease-free survival and possible cure, BMT should be considered for children with ALL presenting poor-prognostic features, particularly certain chromosomal translocations [t(4;11), t(9;22)], very high WBC counts, notably if associated with a non-T immunophenotype, and, perhaps, a poor response to initial therapy with corticosteroids (CS), or infants less than 6 months of age.

Nordic Mantle Cell Lymphoma (MCL) Project: Preemptive Rituximab Treatment of Molecular Relapse Following Autotransplant Can Reinduce Molecular Remission and Prolonged Disease-Free Survival.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2429-2429
Author(s):  
Christian H. Geisler ◽  
Erkki Elonen ◽  
Arne Kolstad ◽  
Anna Laurell ◽  
Lone B. Pedersen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
High Dose ◽  
Clinical Relapse ◽  
Relapse Free Survival ◽  
Molecular Remission ◽  
Free Survival ◽  
Mantle Cell ◽  
Disease Free

Abstract The 2nd. Nordic Lymphoma Group mantle cell lymphoma (MCL2) protocol has demonstrated the importance of Ara-C and Rituximab in the induction chemotherapy and stem-cell mobilisation before high-dose therapy and autologous stem-cell transplant (1). By July 2005, 128 patients (83% stage IV) had completed protocol treatment consisting of 3 series of R-CHOP and 3 series of R-Ara-C, stem-cell harvest and high-dose therapy with BEAM/BEAC with ASCT. The 5-year failure-free and overall survival is 50% and 83% respectively, significantly higher than the historic control group of the Nordic MCL1 protocol with the same treatment without HD-Ara-C and Rituximab (P<0.0001). Patients with a molecular marker (t(11;14) or clonal IgH rearrangement) identified at the time of diagnosis in bone marrow and blood, undergo regular molecular follow-up posttransplant,. Patients who turn PCR-positive or increase their qPCR signal, without clinical disease, are offered preemptive treatment with Rituximab 375 mg/m2 Wx4. Of 75 patients with molecular markers who had completed treatment, 55 remain PCR-negative and 20 have become/remained PCR-pos. posttransplant. Clinical relapse ocurred significantly more often in the latter group (11 of 20) than in the PCR-neg. patients (4 of 55) (P<0.0001) (Fig.1). Ten of the 20 PCR-positive patient did not receive preemptive rituximab: five due to immediate clinical relapse, 2 due to stable qPCR signals, one due to protocol error and two await treatment. Of 10 patients who did receive preemptive rituximab 8 again became PCR-negative and 2 remain PCR-positive. Six of the 10 Rituximab treated patients remain in clinical and molecular remission 200–600 days after the Rituximab treatment (Fig. 2). Conclusions: In MCL, molecular relapse is a harbinger of imminent clinical relapse, whereas continuous molecular remission is associated with prolonged disease-free survival (89% at 4 years) Rituximab preemptive treatment can reinduce molecular remission and may delay clinical relapse. Following molecular relapse, only Rituximab treated patients (6 of 8 evaluable) remain disease-free. FIG. 1. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL ACC. TO MOLECULAR STATUS POSTTRANSPALNT FIG. 1. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL ACC. TO MOLECULAR STATUS POSTTRANSPALNT FIG. 2. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL FROM TIME OF MOLECULAR RELAPSE. FIG. 2. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL FROM TIME OF MOLECULAR RELAPSE.

Mantle cell lymphoma (MCL): Induction therapy with HyperCVAD/High-dose methotrexate and cytarabine (M-C) (±rituximab) improves results of autologous stem cell transplant in first remission

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7511-7511 ◽  
Author(s):  
J. Vose ◽  
F. Loberiza ◽  
P. Bierman ◽  
G. Bociek ◽  
J. Armitage
Keyword(s):  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Disease Free Survival ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Disease Free

7511 Background: Although patients (pts) with MCL have a high response rate to standard chemotherapy, they continue to relapse with no plateau in long term disease-free survival. The use of dose intense induction therapy such as HyperCVAD (M-C) ±Rituximab(R) and high-dose therapy and stem cell may improve these results. In this analysis the outcomes of pts receiving a standard anthracycline induction therapy or HyperCVAD(M-C)(±R) then followed by a stem cell transplant in first complete (CR1) or partial remission (PR1) were compared. Methods: Between 6/91 and 11/05, 124 pts with MCL received high-dose chemotherapy and a stem cell transplant. Of these pts, 80 received an autologous stem cell transplant in CR1 (N = 47) or PR1 (N = 33). A standard anthracycline based CHOP-like (±R) induction therapy was given to 48 pts compared with 32 pts who received HyperCVAD(M-C)(±R) prior to transplant. Results: The median age of pts was 56 years (range 33–70). The male:female ratio was 33:57. Bone marrow involvement prior to conditioning was present in 52% of pts. An elevated lactic dehydrogenase (LDH) was present in 58% of pts. 65% of patients received one prior chemotherapy before coming to stem cell transplant. The median follow up of pts is 38 months (range 3–143). Progression-free survival (PFS) and overall survival (OS) are outlined in table 1 . Characteristics associated with an improved OS by multivariate analysis included receiving HyperCVAD induction (p = 0.04), transplant in CR1 (p = 0.009), ≤ 3 prior chemotherapy regimens (p = 0.02) and no B symptoms at transplant (p = 0.05). Conclusions: To improve the long term disease free survival for pts with MCL, Hyper-CVAD(M-C)(±R) induction should be given to eligible patients with autolgous stem cell transplantation in CR1. [Table: see text] No significant financial relationships to disclose.

No difference in graft-versus-host disease, relapse, and survival comparing peripheral stem cells to bone marrow using unrelated donors

Blood ◽  
2001 ◽  
Vol 98 (6) ◽  
pp. 1739-1745 ◽  
Author(s):  
Mats Remberger ◽  
Oolle Ringdén ◽  
Igor-Wolfgang Blau ◽  
Hellmut Ottinger ◽  
Bernhard Kremens ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Free Survival ◽  
Graft Versus Host ◽  
Unrelated Donors ◽  
Disease Free

Abstract The clinical results in 107 patients receiving a peripheral blood stem cell (PBSC) graft mobilized by granulocyte colony-stimulating factor (G-CSF) from HLA-A, -B, and -DR–compatible unrelated donors were compared to 107 matched controls receiving unrelated bone marrow (BM) transplants. Engraftment was achieved in 94% of the patients in both groups. The PBSC graft contained significantly more nucleated cells, CD34+, CD3+, and CD56+ cells (P < .001), and resulted in a significantly shorter time-to-neutrophil (15 versus 19 days) and platelet engraftment (20 versus 27 days), compared to the BM control group (P < .001). Probabilities of acute graft-versus-host disease (GVHD) grades II to IV were 35% and 32% (not significant [NS]) and of chronic GVHD 61% and 76% (NS) in the PBSC and BM groups, respectively. There was no difference between the 2 groups in bacteremia, cytomegalovirus reactivation or disease, and fungal infection. The 3-year transplant-related mortality (TRM) rates were 42% in the PBSC group and 31% in the BM controls (P = .7) and the survival rates were 46% and 51%, respectively. The probability of relapse was 25% and 31% in both groups (NS), resulting in disease-free survival rates of 43% in the PBSC group and 46% in the BM controls (NS). In the multivariate analysis, early disease, acute GVHD grade 0 to I, and presence of chronic GVHD were independent factors associated with a better disease-free survival in this study. PBSC from HLA-compatible unrelated donors can be used safely as an alternative to BM for stem cell transplantation.

Early Mortality of Newly Diagnosed Adult Acute Promyelocytic Leukemia Treated with the AIDA Protocol.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4617-4617
Author(s):  
George Gortzolidis ◽  
Athanasios Zomas ◽  
Theodore Marinakis ◽  
Evridiki Michalis ◽  
Athanasios Galanopoulos ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Early Mortality ◽  
Induction Phase ◽  
Molecular Remission ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

Abstract APL represents a particular subtype of acute myeloid leukemia with characteristic clinical features, as well as specific immunophenotypic, cytogenetic and molecular findings owing to the chromosomal translocation t(15;17). Anthracycline-based chemotherapy and All-Trans Retinoid Acid (ATRA) became the cornerstone of APL treatment by improving significantly the long term outcome of patients, even though there is some controversy regarding the impact of this combination on the mortality of the induction phase. Herein, we analysed retrospectively the outcome of 16 consecutive adult APL patients who were diagnosed and treated in our Unit from 12/1998 to 10/2004. The analysis focuses more on the parameters of treatment-related mortality, cause of death and disease-free survival post AIDA chemotherapy. All patients were suffering from the classical form of APL and were homogeneously treated as follows: induction consisted of ATRA p.o. and idarubicin i.v. at conventional doses of 45mg/m2/d, from D1 to CR and 12mg/m2/d, D2,4,6,8 (total of 4 infusions), respectively. Dose modifications for elderly individuals were not allowed. Complete remitters were consolidated with 3 courses of chemotherapy without ATRA, where as non-remitters were taken off protocol and received other therapy. Patients in continuing hematological and molecular remission at the end of consolidation were administered maintenance therapy for 2 years with oral 6-MP at 90mg/m2/d, oral MTX weekly at 15mg/m2 and ATRA for 15 days every 3 months. In all cases, the morphological diagnosis of APL was confirmed by chromosome and immunophenotypic analysis of blasts in addition to molecular studies. The median age of our cohort was 55 years (range 31–78) and the male/female ratio was 12/4. Three patients (3/16, 19%) were ≥ 65 years at diagnosis. Two cases (2/16, 12%) presented with a leukocyte count of ≥10 x 103/mm3 while the median Wbc at presentation was 6.5 x 103/mm3. All cases had either clinical (haemorrhagic) or laboratory evidence of disseminated intravascular coagulation. Six patients (6/16, 37%) deceased during the induction phase from pulmonary bleeding (2 cases,days 8 and 13 respectively), intracerebral bleeding (1 case,day 6), myocardial infarction-cardiac arrest (1 case,day 5), respiratory distress syndrome secondary to ATRA syndrome (1 case, day 17), and sepsis-induced hemophagocytosis syndrome (1 case, day 38). All ten out of the 16 (63%) surviving patients achieved hematological and molecular CR and remain to date relapse-free in excellent clinical condition. The median overall survival and disease-free survival for the whole group is 25 months but the same parameters for the surviving patients is better at 42 months. Our results corroborate that in APL the AIDA protocol together with maintenance treatment is highly effective in producing sustained haematological and molecular remission. Despite this excellent antileukaemic activity, early mortality (37% in our cohort) caused chiefly by fatal bleeding and thrombotic events (four patients) limits considerably patient survival and deserves further research in order to improve long-term outcome.

Allogeneic bone marrow transplantation as therapy for primary induction failure for patients with acute leukemia.

1991 ◽  
Vol 9 (9) ◽  
pp. 1570-1574 ◽  
Author(s):  
S J Forman ◽  
G M Schmidt ◽  
A P Nademanee ◽  
M D Amylon ◽  
N J Chao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
High Dose ◽  
Allogeneic Bone ◽  
Primary Therapy ◽  
Free Survival ◽  
Disease Free

The survival of patients with acute leukemia who do not achieve a remission with primary therapy is very poor. High-dose chemoradiotherapy followed by allogeneic bone marrow transplantation (BMT) has been shown to be effective therapy for patients with acute and chronic leukemia. Therefore, we determined the long-term disease-free survival of patients who did not achieve a remission and were then treated with high-dose therapy and bone marrow allografting from matched sibling donors. Twenty-one patients (median age, 28 years) who did not achieve a remission with induction chemotherapy were subsequently treated with allogeneic BMT. After BMT, 90% achieved a complete remission. Six died of complications of the therapy, and six patients relapsed between 27 and 448 days after BMT. Nine patients (43%; median age, 25 years) are alive between 556 and 4,174 days after BMT. The cumulative probability of disease-free survival at 10 years is 43%. This study suggests that allogeneic BMT can be an effective therapy to achieve long-term control of acute leukemia, even in those patients who do not achieve a remission with primary therapy.

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