Results of the vincristine, doxorubicin, and dexamethasone regimen in adults with standard- and high-risk acute lymphocytic leukemia.

1990 ◽  
Vol 8 (6) ◽  
pp. 994-1004 ◽  
Author(s):  
H M Kantarjian ◽  
R S Walters ◽  
M J Keating ◽  
T L Smith ◽  
S O'Brien ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Lymphocytic Leukemia ◽  
Autologous Bone Marrow Transplantation ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Older Age ◽  
Leukemic Cells ◽  
High Dose ◽  
Long Term Outcome

One hundred five untreated adult patients with acute lymphocytic leukemia (ALL) were entered on the vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and Decadron (dexamethasone; Merck Sharp and Dohme, West Point, PA) (VAD) regimen. Induction therapy with VAD and VAD plus cyclophosphamide (CVAD) was followed by a 2-year rotating maintenance program with multiple antileukemic combinations, and included early intensifications with Adriamycin and high-dose cytarabine (ara-C) and a late intensification with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologous bone marrow transplantation (BMT). Duration of therapy was 24 to 30 months. Eight-eight patients (84%) achieved complete remission (CR) with VAD-CVAD, and 94 (90%) ultimately had CR with continuation of the maintenance as planned. Induction mortality was 3%; only half of the patients required prolonged hospitalization of 1 week or longer, or intravenous antibiotics. Maintenance therapy was given to 79 patients, while nine with histocompatibility locus antigen (HLA)-matched related donors underwent allogeneic BMT. The median remission duration was 22 months, and the median survival was 19 months. Factors associated with significantly worse CR rates were older age, the presence of hypoalbuminemia or hyperbilirubinemia, L2 or L3 morphology, and myeloid markers on leukemic cells. Those associated with significantly worse remission durations were the presence of elevated leukocyte or absolute peripheral blast counts, Philadelphia chromosome (Ph)-positive or B-cell ALL, L2 morphology, and more than one course to achieve CR. Patients could be divided into standard-risk ALL (28% of patients) and high-risk ALL (72% of patients) with long-term remission rates of 70% versus less than 30%. The 26 patients who underwent CBV autologous BMT had similar long-term outcome compared with 21 patients who did not (older age, medical contraindications, or socioeconomic problems). The presence or absence of myeloid markers on leukemic cells did not affect long-term prognosis. We conclude that VAD therapy is a well-tolerated effective induction regimen. High-risk ALL patients require alternative maintenance investigational approaches.

Results of Treatment With Hyper-CVAD, a Dose-Intensive Regimen, in Adult Acute Lymphocytic Leukemia

2000 ◽  
Vol 18 (3) ◽  
pp. 547-547 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Susan O’Brien ◽  
Terry L. Smith ◽  
Jorge Cortes ◽  
Francis J. Giles ◽  
...  
Keyword(s):  
B Cell ◽  
Acute Lymphocytic Leukemia ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Prognostic Models ◽  
Poor Performance Status ◽  
High Dose ◽  
Cell Disease ◽  
Adult Acute Lymphocytic Leukemia ◽  
Intensive Regimen

PURPOSE: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37% were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%. Leukocytosis of more than 30 × 109/L was found in 26%, Philadelphia chromosome–positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). RESULTS: Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91% v 75%, P < .01) and CR rate after one course (74% v 55%, P < .01) and better survival (P < .01), and a smaller percentage had more than 5% day 14 blasts (34% v 48%, P = .01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy. CONCLUSION: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.

Long-Term Outcome of High-Dose Sequential Chemotherapy with Autografting (i-HDS) in Follicular Lymphoma at Diagnosis: An Update of the Prospective Multicenter Consecutive Trial of the "Gruppo Italiano Trapianto Di Midollo Osseo" (Gitmo).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 903-903
Author(s):  
Marco Ladetto ◽  
Sonia Vallet ◽  
Paolo Corradini ◽  
Fabio Benedetti ◽  
Umberto Vitolo ◽  
...  
Keyword(s):  
High Risk ◽  
Residual Disease ◽  
Elevated Serum ◽  
Stage Iv ◽  
Experimental Treatment ◽  
High Dose ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Treatment Implementation

Abstract Introduction. i-HDS is a promising though experimental treatment for FL patients at diagnosis. We have published that i-HDS is feasible also in the context of a multicenter trial with limited toxicity and promising results (Ladetto et al, Blood, 2002). This analysis is an update at 42 months from the previous closing date. Particular attention has been devoted to late toxicities and outcome according to molecular remission (MR). Patients and methods. 92 untreated patients aged 18–60 years with stage III-IV FL requiring treatment were enrolled by 20 Italian centers between 1997 and 1999 and evaluated on an intention-to-treat basis. Inclusion criteria have been previosly described. Clinical features at diagnosis were: Ann Arbor stage IV: 84%; BM involvement: 80%; extranodal and extra-BM disease: 55%; bulky mass: 51%; elevated serum LDH: 37%; "B" symptoms: 30%; leukemic disease: 12%; aaIPI ≥ 2: 37%. The i-HDS schedule included 2APO, 2DHAP, Etoposide 2g/sqm, Methotrexate 8g/sqm and Cyclophosphamide 7g/sqm with PBPC collection. The myeloablative regimen was Mitoxantrone 60mg/sqm + Melphalan 180mg/sqm followed by 5–8x106 CD34+ cells/kg. Minimal residual disease analysis with the bcl-2/IgH rearrangement was available in 47% of patients. Results: 87% of patients completed the planned treatment. CR rate was 88%. Currently the median follow-up is 62 months. Late toxic effects included five myelodysplastic syndromes and /or secondary leukemias (MDS/2AL) all occurring within two years from the end of treatment. In 4 of 5 cases MDS/2AML occurred in subjects already re-treated for disease relapse. Two fatal solid tumors (one gastric cancer and one lung cancer) were also recorded. Long-term hematopoietic fuction was satisfactory in all patients not developing MDS/2AML. Heart failure occurred in three patients, always manageable with oral medical treatment. The projected overall survival and progression-free survival (PFS) at 7,5 years are 74% and 56%. Notably, following i-HDS, patients with aaIPI≥2 had an outcome comparable to those with aaIPI ≤ 1 (p=NS). Attainement of MR in the first year following i-HDS was highly predictive even for the long term outcome. Among patients achieving MR the relapse rate (RR) was 13% while in those failing to achieve MR was 81% (p<0001). Conclusions. This long-term analysis indicates the following: a) i-HDS allows long-term PFS in 56% of advanced FL patients regardless of the aaIPI. This result compares favorably with those achieved with Rituximab-free non-intensified therapy at least for high-risk patients; b) MR achievement is a powerful indicator for prolonged PFS; c) although severe side effects occurred in this series, relapse remains the major cause of treatment failure. Thus, treatment implementation is required. Rituximab inclusion is probably one of the most feasible approaches, suitable for multicenter trials. The new GITMO trial, comparing CHOP vs i-HDS (both supplemented with Rituximab), currently ongoing for high-risk (aaIPI≥2) FL patients, will help clarifying wheter dose-intensification has still a role in the monoclonal antibody era.

De-Intensification of the Chemotherapy Did Not Affect the Outcome of Ph-Positive Acute Lymphocytic Leukemia Patients in the Era of Tyrosine Kinase Inhibitors

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2805-2805
Author(s):  
Olga A. Gavrilina ◽  
Elena N. Parovichnikova ◽  
Vera V. Troitskaya ◽  
Andrey N. Sokolov ◽  
Larisa A. Kuzmina ◽  
...  
Keyword(s):  
Complete Remission ◽  
Acute Lymphocytic Leukemia ◽  
Kinase Inhibitors ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Free Survival ◽  
Disease Free

Abstract Introduction. For more than a decade it's postulated that the addition oftyrosine kinase inhibitors (TKI) to chemotherapy has dramatically improved the long term outcome in Ph-positive adult acute lymphoblastic leukemia (Ph+ ALL). Nevertheless whether do we need chemotherapy at all and if yes - how intensive it should be, is still the matter of debates. The only randomized trial addressing this issue (GRAAL, Blood 2015, 125: 3711-3719) has demonstrated the lack of benefit of more intensive induction at all checkpoints: complete remission (CR) rate, major molecular complete remission (MMolCR), molecular complete remission (MolCR), progression disease (PD) and resistance. We have conducted two consecutive trials in Ph+ ALL aiming to evaluate the efficacy of more and less intensive chemotherapy approach in combination with constant non-stop 600 mg Imatinib application. Aim. Toanalyze of the protocol RALL-2009 with ITK and RALL-Ph+-2012 effectiveness in patients with Ph+ ALL. The primary objective was the major molecular complete remission (MMolCR) rate after induction (70th day), patients being then eligible for allogeneic stem cell transplantation (SCT) if they had a donor, or autologous SCT if in MMolR and no donor. Patients and methods. Since Jan 2010 till July 2016, 120 new cases of ALL were verified in our National Research Center for Hematology with 68 (56,7%) of them being B-cell precursors ALL and 25 diagnosed as Ph-positive (36,8%). Since 2010 till 2012, 10 Ph+ ALL pts (median age 35 years (19-68), m/f (50%)/(50%), CNS disease=1, WBC> 30*109/l=5(50%), bcr/abl transcript p190/p210/p190+210 6(60%)/3(30%)/1(10%)) were treated according to RALL-2009 protocol (ClinicalTrials.gov public site; NCT01193933) with parallel Imatinib. This protocol includes 8 cytostatic drugs and no intervals between treatment phases. Since 2012 till now 15 other pts (median age 40 years (17-61); m/f 7(46,7%)/8(53,3%); CNS disease=1, WBC>30*109/l=5(33,3%), bcr/abl transcript p190/p210/p190+210 9(60%)/5(33%)/1(7%)) were included in RALL- Ph+-2012 protocol, based mainly on 600 mg Imatinib with prednisolone, VNCR, L-asp, followed by 6-MP and MTX. Both protocols suggested the shift to Dasatinib (100-140 mg) after non-achievement of MolCR at day 70 of treatment. MolCR was stated if no bcr/abl chimeric transcript was detected by PCR with 10-4 sensitivity. All patients were considered as candidates for allogeneic HSCT if HLA-identical donor was available. Results. At day 70th disregarding the chemotherapy intensity there was 40% of MolCR on both protocols (RALL-2009 - n=4 and RALL-2012 - n=6). No death within 2 months of induction/consolidation were registered on less intensive protocol in comparison with 2 cases on RALL-2009. Hematological CR was achieved in all pts (except two early deaths on RALL-2009) - 23 of 25 (92%). There was one autologous HSCT in older pts, included in RALL-2012 (n=3, aGVHD and severe infections, at a median +4 months after HSCT and more than 12 months of CR duration). The 3y OS, DFS and relapse probability (RP) for all 25 pts constituted 37,8%, 32,5% and 52,1% (Fig. 1). The long-term outcome on both protocols (RALL-2009 and RALL-2012) was similar: OS - 45% vs 27,7% (p=0,27), DFS - 45% vs 22,1% (p=0,94), RP - 35,7% vs 57% (p=0,29), respectively (Fig.2). Conclusion. De-intensification of the chemotherapy does not affect the effectiveness of the therapy Ph-positive acute lymphocytic leukemia in era of the tyrosine kinase inhibitors. We haven't seen differences in achievement of molecular remission when we deescalated chemotherapy (40% vs. 40%). However, when we reduced toxicity of the chemotherapy in ALL-2012 protocol, we were able to realize more extra allo-BMT and it could improve long-term results of the therapy Ph+ ALL. Figure Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL protocols. Figure. Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL protocols. Figure Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL-2009 and RALL-2012 protocols. Figure. Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL-2009 and RALL-2012 protocols. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Difficult-to-Treat del 17 p Patient—A Case Report in Chronic Lymphocytic Leukemia

Medicina ◽  
2021 ◽  
Vol 58 (1) ◽  
pp. 33
Author(s):  
Ana-Maria Moldovianu ◽  
Ana Manuela Crisan ◽  
Zsofia Varady ◽  
Daniel Coriu
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Lymphocytic Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Risk Patients ◽  
Potential Benefits

Chronic lymphocytic leukemia (CLL) treatment strategies have evolved to include mechanism-driven drugs but now raise new questions regarding their optimum timing and sequencing. In high-risk patients, switching from pathway inhibitors to allogeneic stem cell transplantation (allo-HCT) is still a matter of intense debate. We report the case of a CLL patient with 17 p deletion treated with ibrutinib as a bridge to allo-HCT. Early relapse after allo-HCT urged the initiation of salvage therapy, including donor lymphocytes infusions, ibrutinib, and venetoclax. We aim to outline and discuss the potential benefits of novel therapies, the current role of allo-HCT in CLL, drug timing and sequencing, and the unmet need to improve the long-term outcome of high-risk CLL patients.

scholarly journals Establishment and characterization of a cell line, TOM-1, derived from a patient with Philadelphia chromosome-positive acute lymphocytic leukemia

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 990-998 ◽  
Author(s):  
M Okabe ◽  
S Matsushima ◽  
M Morioka ◽  
M Kobayashi ◽  
S Abe ◽  
...  
Keyword(s):  
Cell Line ◽  
Messenger Rna ◽  
Acute Lymphocytic Leukemia ◽  
Bone Marrow Cells ◽  
Germ Line ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Chromosome 22

Abstract A new Philadelphia chromosome (Ph1)-positive cell line, designated TOM- 1, was derived from bone marrow cells of a patient with Ph1-positive acute lymphocytic leukemia (ALL). The TOM-1 cells were positive for Ia and B1 antigens and terminal deoxynucleotidyl transferase (TdT) but negative for common ALL antigen. Although neither surface Ig nor cytoplasmic Ig was detected, the TOM-1 cells contained rearranged immunoglobulin-H chain genes but retained germ-line kappa chain and germ-line T cell receptor beta-chain genes. These results indicate that the TOM-1 cells reside as the progenitor of pre-B cells. We have investigated the chromosome 22 breakpoint and c-abl gene expression in the TOM-1 cells. We found that the breakpoint on chromosome 22 was within the breakpoint cluster region (bcr) in the TOM-1 cells. We also found the breakpoints within or near bcr in four of six Ph1-positive ALL cases, similar to the findings in Ph1-positive CML cases. Amplification of the c-abl gene was not detected in the TOM-1 cells. The leukemic cells isolated from a patient with CML in myeloid crisis contained a novel 8-kilobase (kb) abl-related messenger RNA (mRNA), but the TOM-1 cells contained c-abl transcripts of only normal sizes, despite the fact that they showed the bcr gene rearrangement.

scholarly journals Dose Intensive Rituximab and High-Dose Methylprednisolone in Elderly or Unfit Patients with Relapsed Chronic Lymphocytic Leukemia

Medicina ◽  
2019 ◽  
Vol 55 (11) ◽  
pp. 719
Author(s):  
Pileckyte ◽  
Valceckiene ◽  
Stoskus ◽  
Matuzeviciene ◽  
Sejoniene ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Meaningful Improvement ◽  
Free Survival ◽  
High Dose Methylprednisolone ◽  
Unfit Patients

Background and Objectives: BTK and BCL2 inhibitors have changed the treatment paradigms of high-risk and elderly patients with chronic lymphocytic leukemia (CLL), but their long-term efficacy and toxicity are still unknown and the costs are considerable. Our previous data showed that Rituximab (Rtx) and high-dose methylprednisolone (HDMP) can be an effective and safe treatment option for relapsed high-risk CLL patients. Materials and Methods: We explored the efficacy and safety of a higher Rtx dose in combination with a shorter (3-day) schedule of HDMP in relapsed elderly or unfit CLL patients. Results: Twenty-five patients were included in the phase-two, single-arm trial. The median progression free survival (PFS) was 11 months (range 10–12). Median OS was 68 (range 47–89) months. Adverse events (AE) were mainly grade I–II° (77%) and no deaths occurred during the treatment period. Conclusions: 3-day HDMP and Rtx was associated with clinically meaningful improvement in most patients. The median PFS in 3-day and 5-day HDMP studies was similar and the toxicity of the 3-day HDMP schedule proved to be lower. The HDMP and Rtx combination can still be applied in some relapsed high-risk and elderly or unfit CLL patients if new targeted therapies are contraindicated or unavailable. (ClinicalTrials.gov identifier: NCT01576588).

scholarly journals Establishment and characterization of a cell line, TOM-1, derived from a patient with Philadelphia chromosome-positive acute lymphocytic leukemia

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 990-998 ◽  
Author(s):  
M Okabe ◽  
S Matsushima ◽  
M Morioka ◽  
M Kobayashi ◽  
S Abe ◽  
...  
Keyword(s):  
Cell Line ◽  
Messenger Rna ◽  
Acute Lymphocytic Leukemia ◽  
Bone Marrow Cells ◽  
Germ Line ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Chromosome 22

A new Philadelphia chromosome (Ph1)-positive cell line, designated TOM- 1, was derived from bone marrow cells of a patient with Ph1-positive acute lymphocytic leukemia (ALL). The TOM-1 cells were positive for Ia and B1 antigens and terminal deoxynucleotidyl transferase (TdT) but negative for common ALL antigen. Although neither surface Ig nor cytoplasmic Ig was detected, the TOM-1 cells contained rearranged immunoglobulin-H chain genes but retained germ-line kappa chain and germ-line T cell receptor beta-chain genes. These results indicate that the TOM-1 cells reside as the progenitor of pre-B cells. We have investigated the chromosome 22 breakpoint and c-abl gene expression in the TOM-1 cells. We found that the breakpoint on chromosome 22 was within the breakpoint cluster region (bcr) in the TOM-1 cells. We also found the breakpoints within or near bcr in four of six Ph1-positive ALL cases, similar to the findings in Ph1-positive CML cases. Amplification of the c-abl gene was not detected in the TOM-1 cells. The leukemic cells isolated from a patient with CML in myeloid crisis contained a novel 8-kilobase (kb) abl-related messenger RNA (mRNA), but the TOM-1 cells contained c-abl transcripts of only normal sizes, despite the fact that they showed the bcr gene rearrangement.

Impact of Posttransplant Imatinib Administration on Philadelphia-Chromosome Positive Acute Lymphocytic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4416-4416
Author(s):  
Satoshi Nishiwaki ◽  
Koichi Miyamura ◽  
Hisashi Sakamaki ◽  
Shinji Nakao ◽  
Hideo Harigae ◽  
...  
Keyword(s):  
Fundamental Solution ◽  
Acute Lymphocytic Leukemia ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Event Free Survival ◽  
Early Administration ◽  
Free Survival ◽  
Prophylactic Administration ◽  
Philadelphia Chromosome Positive

Abstract Philadelphia-chromosome positive acute lymphocytic leukemia (Ph+ALL) is an intractable disease. After the development of imatinib, a tyrosine kinase inhibitor, the outcome of chemotherapy, especially remission induction rate, has been improved. Its long-term prognosis is, however, still poor, mainly because of high relapse rate, and therefore allogeneic stem cell transplantation (allo-SCT) is considered to be the only curative option. Recently, adopting the idea of minimal residual disease (MRD) in a treatment strategy of Ph+ALL as well as chronic myeloid leukemia (CML), it was reported that even in hematologically complete remission (CR), positive MRD at allo-SCT was a strong predictor for relapse after allo-SCT. Although it is ideal to perform allo-SCT in MRD-negative condition, it is sometimes difficult to achieve such treatment effect, despite the administration of imatinib. There are some reports dealing with posttransplant imatinib administration, but its efficacy and administration methods are still controversial. To evaluate the effect of posttransplant imatinib administration, we retrospectively analyzed 34 Ph+ALL patients who received allo-SCT at 7 transplant centers in Japan between January 1989 and September 2007. Study admission criteria were allo-SCT for the first time, non-manipulation and MRD positive at allo-SCT. Median age at allo-SCT was 40 years old, 18 patients were transplanted in hematological CR, 14 patients were transplanted from unrelated donors and 20 patients from relative donors. Seven out of 34 patients received posttransplant imatinib administration. We proposed two strategies for posttransplant imatinib administration. One was early administration, where imatinib was administered upon detecting MRD after allo-SCT. The other was prophylactic administration, where imatinib was administered as soon after allo-SCT as possible. Overall survival was significantly better in patients with posttransplant administration (29.6% in patients without posttransplant imatinib vs. 66.7% in those with posttransplant imatinib at 3 years, p=0.03). In contrst, there was no significant difference in event-free survival (EFS) between two groups (29.6% in patients without posttransplant imatinib vs. 0% in those with posttransplant imatinib at 3 years, p=0.29).(Figure) As for details of MRD in patients with posttransplant imatinib administration, the duration of negative MRD was 9 months, 6 months, and 2 months or more in the early administration group, while in the prophylactic administration group it was 29 months, 12 months, and 9 months or more. It seemed that the duration of negative MRD was longer in the prophylactic group, but in all patients whose observation periods were longer than 1 year, MRD became positive in both groups and this lead to hematological relapse. The fact that posttransplant imatinib administration, even prophylactic administration, was no significant effect on event-free survival revealed the limitation of imatinib administration after allo-SCT. Although it is a great thing to achieve longer duration of negative MRD, posttransplant imatinib administration could not be a fundamental solution for Ph+ALL patients whose MRD was positive at allo-SCT. Considering the cure for Ph+ALL, MRD at allo-SCT has a profound impact on long-term EFS and posttransplant intervention seems to have limitation. To achieve a fundamental solution, the key would be to achieve negative MRD at allo-SCT, for example, by using new drugs, like nilotinib, dasatinib and other secondgeneration tyrosine inhibitors in case imatinib was inadequate to achieve negative MRD. MRD-based strategy is essential for a cure of Ph+ALL.

scholarly journals Chromosomal abnormalities identify high-risk and low-risk patients with acute lymphoblastic leukemia

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 415-420 ◽  
Author(s):  
CD Bloomfield ◽  
AI Goldman ◽  
G Alimena ◽  
R Berger ◽  
GH Borgstrom ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Chromosomal Abnormalities ◽  
Lymphoblastic Leukemia ◽  
International Workshop ◽  
Philadelphia Chromosome ◽  
Normal Karyotype ◽  
Term Outcome ◽  
Long Term Outcome

The importance of banded chromosome analyses in predicting long-term outcome in acute lymphoblastic leukemia (ALL) was evaluated in this follow-up study of 329 patients from the Third International Workshop on Chromosomes in Leukemia. Patients were divided into ten groups according to pretreatment karyotype: no abnormalities, one of the following structural abnormalities [the Philadelphia chromosome, translocations involving 8q24,t(4;11), 14q+, 6q-] or, in the remaining cases, modal number [less than 46, 46, 47 to 50, greater than 50]. Achievement and duration of complete remission (CR) and survival differed among chromosome groups (P less than .0001). Karyotype was an independent prognostic factor for duration of first CR and survival, even when age, initial leukocyte count (WBC), French-American-British (FAB) type, and immunologic phenotype were considered. Among adults, prolonged remission and survival were uncommon in all chromosome groups. Only in the normal karyotype group was median survival even two years. Among children, striking differences in long-term remission and survival were seen depending upon karyotype. Children in the greater than 50 group did best, with 70% remaining in first CR for a median duration in excess of five years. Children in the 47–50, 6q-, and normal karyotype groups also had prolonged survivals. In contrast, certain translocations [t(9;22)(q34;q11), t(4;11)(q21;q14–23), t(8;14)(q24;q32)] identified children who had short survivals, even in the presence of favorable prognostic factors including a low WBC, L1 morphology, and non-T, non-B immunologic phenotype. We conclude that chromosome analysis is required at diagnosis in patients with ALL, and that children with these specific translocations should be managed as having high-risk ALL.

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