Treatment of High-Risk (HR) Philadelphia Chromosome-Negative (Ph-) Adult Acute Lymphoblastic Leukemia (ALL) According to Baseline Risk Factors and Minimal Residual Disease (MRD). Results of the PETHEMA ALL-AR-03 Trial.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3291-3291
Author(s):  
Josep-Maria Ribera ◽  
Albert Oriol ◽  
Mireia Morgades ◽  
Josep Sarra ◽  
Pau Montesinos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Baseline Risk ◽  
High Dose ◽  
Consolidation Therapy ◽  
Wbc Count ◽  
Delayed Consolidation

Abstract Background and aim: Current therapeutic protocols for adult ALL consider MRD together with the baseline risk factors (age, WBC count, immunophenotype, cytogenetics) and speed in response to therapy for treatment decisions. On the other hand, the systematic use of allogeneic SCT for all adult patients (pts) with Ph- HR-ALL is still a matter of debate. The aim of the prospective study ALL-AR-03 from the Spanish PETHEMA Group was to evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance and MRD levels (assessed by cytofluorometry at the end of induction and consolidation therapy) in HR Ph- adult ALL patients. Patients and methods: HR ALL included one or more of the following baseline parameters: age 30–60 yr, WBC count >25x109/L and 11q23 or MLL rearrangements. Induction therapy included vincristine, prednisone and daunorubicin for 4 weeks. In pts with slow cytologic response to therapy (≥10% blasts in bone marrow assessed on d14) intensified induction with high dose ARA-C and mitoxantrone was administered. Early consolidation therapy included 3 cycles with rotating cytotoxic drugs including high-dose methotrexate, high-dose ARA-C and high-dose asparaginase. Pts. with slow cytologic response on d14 or MRD level >0.05% after consolidation were assigned to allogeneic SCT (related or unrelated) and those with standard cytologic response on d14 and MRD level <0.05% after consolidation received 3 additional cycles of delayed consolidation (identical to those of early consolidation) followed by maintenance therapy up to 2yr in CR. Results: On June 2008,192 patients were evaluable (mean (SD) age 37(10) yr, 105 males, 119 precursor B-ALL, 73 T-ALL, WBC count 65(99) x109/L). Induction death: 17(9%), resistance: 12 (6%), CR: 163 (85%). MRD<0.1% was observed in 64% of CR patients. Early consolidation was completed in 126 patients. MRD<0.05% was observed in 65% at the end of consolidation. On June 2008, allogeneic SCT was performed to 30 pts (15 from HLA-identical siblings and 15 MUD), TRM 11 pts, relapse 4, CCR 15. Delayed consolidation and maintenance was administered to 79 pts (toxic death 4 pts, relapse 21, CCR 54). Four-yr DFS for the whole series was 36±7% (37±19% for pts assigned to SCT and 56±12% for those assigned to chemotherapy). Slow cytologic response was associated with a lower CR probability and higher induction death. No baseline variable was associated with a higher probability of MRD negativity after induction or consolidation. Conclusions: These results suggest that in HR Ph- adult ALL pts with adequate response to induction and adequate clearance of MDR the results of therapy are not hampered by avoiding allogeneic SCT. Supported by grants P-EF/07 from FIJC and RD 06/0020/1014 from Instituto Carlos III

Treatment of High-Risk (HR) Philadelphia Chromosome-Negative (Ph-) Adult Acute Lymphoblastic Leukemia (ALL) According to Baseline Risk Factors and Minimal Residual Disease (MRD). Results of the PETHEMA ALL-AR-03 Trial Including the Use of Propensity Score (PS) Method to Reduce Assignment Bias.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 322-322 ◽  
Author(s):  
Josep-Maria Ribera ◽  
Albert Oriol ◽  
Mireia Morgades ◽  
Miguel-Angel Sanz ◽  
Pau Montesinos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Lymphoblastic Leukemia ◽  
Response To Therapy ◽  
Baseline Risk ◽  
High Dose ◽  
Consolidation Therapy ◽  
Risk Of Death ◽  
Wbc Count ◽  
Delayed Consolidation

Abstract Abstract 322 Introduction: Current therapeutic protocols for adult ALL consider MRD together with the baseline risk factors (age, WBC count, immunophenotype, cytogenetics) and speed in response to therapy for treatment decisions. On the other hand, the systematic use of allogeneic SCT for all adult patients (pts) with Ph- HR-ALL is still a matter of debate. The aim of the prospective study ALL-AR-03 from the Spanish PETHEMA Group was to evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance (<10% blasts in bone marrow assessed on day 14) and MRD levels (assessed by cytofluorometry at the end of induction –week 5- and consolidation therapy –week 17-) in HR Ph- adult ALL patients. Patients and methods: HR ALL included one or more of the following baseline parameters: age 30–60 yr, WBC count >25×109/L and 11q23 or MLL rearrangements. Induction therapy included vincristine, prednisone and daunorubicin for 4 weeks. In pts with slow cytologic response to therapy intensified induction with high dose ARA-C and mitoxantrone was administered. Early consolidation therapy included 3 cycles with rotating cytotoxic drugs including high-dose methotrexate, high-dose ARA-C and high-dose asparaginase. Pts. with slow cytologic response on d14 or MRD level >0.05% after consolidation were assigned to allogeneic SCT (related or unrelated) and those with standard cytologic response on d14 and MRD level <0.05% after consolidation received 3 additional cycles of delayed consolidation (identical to those of early consolidation) followed by maintenance therapy up to 2yr in CR. Results: On June 2009, 235 HR ALL pts were evaluable [mean (SD) age 37(14) yr, 129 males, 155 precursor B-ALL, 80 T-ALL, WBC count 64(96) ×109/L]. Induction death: 20(8%), resistance: 11 (5%), CR: 202 (87%). Slow cytologic response on d14 was observed in 137/186 (74%) pts, MRD<0.1% at the end of induction was observed in 70% of CR patients and MRD<0.05% was shown in 82% of pts at the end of consolidation. By intention-to treat allogeneic SCT was assigned to 51 pts and delayed consolidation and maintenance to 107 pts. 4-yr DFS and OS probabilities were 40±15% and 49±15%, respectively, for pts assigned to SCT and 49±13% and 64±12%, respectively, for those assigned to chemotherapy. For OS the Cox model including PS showed that patients assigned to allogeneic SCT had a risk of death of 1.27 (95%CI 0.68–2.37) compared to that of the pts assigned to chemotherapy. Patients with MRD<0.1% at the end of induction and <0.05% at the end of consolidation showed a 4-yr DFS and OS of 54±16% and 77±12%, respectively vs. 31±29% and 38±32%, respectively for those with MRD≥0.1% after induction and ≥0.05% after consolidation (p=0.04 and 0.006, respectively). By multivariate analysis, including the type of treatment as covariate, age and slow cytologic response were the prognostic factors for CR, MRD level was associated with DFS, and MRD level and WBC count were the main parameters with influence on OS. Conclusions: These results suggest that in HR Ph- adult ALL pts with adequate response to induction and adequate clearance of MDR after consolidation the results of therapy are not hampered by avoiding allogeneic SCT. MRD is the main prognostic factor for CR, DFS and OS. Supported by grants P-EF/07 from FIJC and RD 06/0020/10556 from RETICS, and PI051490 from FIS, Instituto Carlos III. Disclosures: No relevant conflicts of interest to declare.

Treatment of High-Risk (HR) Philadelphia Chromosome-Negative (Ph-) Adult Acute Lymphoblastic Leukemia (ALL) According to Classical Risk Factors and Minimal Residual Disease (MRD). Interim Results of the PETHEMA ALL-AR-03 Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1872-1872
Author(s):  
Josep Ribera ◽  
Albert Oriol ◽  
Mireia Morgades ◽  
Josep Sarrá ◽  
Salut Brunet ◽  
...  
Keyword(s):  
Risk Factors ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Consolidation Therapy ◽  
Initial Variable ◽  
Therapeutic Protocols ◽  
Wbc Count ◽  
Delayed Consolidation

Abstract Current therapeutic protocols for adult ALL consider MRD together with the classical risk factors (age, WBC count, immunophenotype, cytogenetics and speed in response to therapy) for treatment decisions. The aim of the prospective study ALL-AR-03 from the Spanish PETHEMA Group was to evaluate the feasibility of sequential MRD detection and the response to a differentiated therapy according to MRD levels (assessed by cytofluorometry at the end of induction and consolidation therapy) in HR Ph- adult ALL pts. HR ALL included one or more of the following: age 30–60 yr, WBC count &gt;25×109/L and 11q23 or MLL rearrangements. Induction therapy included VCR, DNR and PDN for 4 wk. In pts with slow cytologic response (≥ 10% blasts in BM assessed on d14) intensified induction with HD-ARA-C and mitoxantrone was administered. Early consolidation therapy included 3 cycles with rotating cytotoxic drugs including HD-MTX, HD-ARA-C and HD-ASP. Pts. with slow cytologic response on d14 or MRD level &gt;0.05% after consolidation were assigned to allogeneic SCT (related or unrelated) and those with standard cytologic response on d14 and MRD level &lt;0.05% after consolidation received 3 additional cycles of delayed consolidation (identical to those of early consolidation) followed by maintenance therapy up to 2yr in CR. On May 2006,119 patients were evaluable (mean (SD) age 37(14) yr, 64 males, 75 precursor B-ALL, 44 T-ALL, WBC 67(87) ×109/L). Induction death 7(%), resistance 20 (%), CR 93 (78%) and MRD&lt;0.1% in 64% were observed. Early consolidation was completed in 63 patients. MRD&lt;0.05% was observed in 77% at the end of consolidation. Allo-SCT was performed in 20 pts (TRM 6, relapse 1, CCR 13) and delayed consolidation and maintenance in 38 (toxic death 2, relapse 7, CCR 29). Two-yr DFS for the whole series was 35±13%. No significant differences were observed between pts receiving chemotherapy or SCT. Slow cytologic response was associated with a lower CR. No initial variable was associated with a higher probability of MRD negativity after induction or consolidation. Neither the negativity of MRD nor the pattern of clearance of MRD were associated with a better DFS. These preliminary results suggest that in HR adult ALL pts with adequate response to induction and adequate clearance of MDR the results of late consolidation and maintenance are not hampered by avoiding allo-SCT.

scholarly journals Post-Remission Treatment with Chemotherapy or Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) of High-Risk (HR) Philadelphia Chromosome-Negative (Ph-neg) Adult Acute Lymphoblastic Leukemia (ALL) According to Minimal Residual Disease (MRD). Preliminary Results of the Pethema ALL-HR-11 Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1333-1333 ◽  
Author(s):  
Josep-Maria Ribera ◽  
Mireia Morgades ◽  
Juana Ciudad ◽  
Pere Barba ◽  
Rodrigo Martino ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Consolidation Therapy ◽  
Hematopoietic Stem ◽  
E Coli ◽  
Preliminary Results ◽  
Post Induction ◽  
Wbc Count ◽  
Delayed Consolidation

Abstract Introduction: Recent studies have shown that young to middle-aged adults who receive a pediatric-inspired chemotherapy regimen for treatment of Ph-neg ALL do not appear to require an alloHSCT if they achieve good response on MRD testing after induction therapy. Patients (pts) who are not good MRD responders achieve better outcomes with alloHSCT than their counterparts who do not receive alloHSCT. However, it is not clear if this approach can be translated to adult ALL pts with HR features at baseline. The aim of the prospective ALL-HR-11 trial from the Spanish PETHEMA Group was to evaluate the response to a differentiated post-induction therapy (chemotherapy or alloHSCT) according to MRD levels (assessed by 8-color, centrally-performed flow cytometry at the end of induction-week 5- and consolidation therapy-week 17-) in HR Ph-neg adult ALL patients. Patients and methods: HR ALL included one or more of the following parameters at baseline: age 30-60 yr, WBC count >30x109/L for B-cell precursor ALL or >100x109/L for thymic T-ALL, pro-B, early or mature T-ALL, 11q23 or MLL rearrangements or complex karyotype. Induction therapy included vincristine, prednisone, daunorubicin and asparaginase (E coli native or PEG according to center availability) for 4 weeks (Induction-1). FLAG-Ida was administered as intensified induction (Induction-2) in pts not achieving CR or those in CR with MRD≥0.1% at the end of induction. For pts in CR and MRD<0.1% early consolidation therapy included 3 cycles with rotating cytotoxic drugs with high-dose methotrexate, high-dose ARA-C and high-dose asparaginase (E coli native or PEG). These pts continued with delayed consolidation (identical to that of early consolidation) followed by maintenance therapy up to 2 yr. in CR if MRD levels after consolidation were <0.01%, otherwise they were assigned to alloHSCT. Pts in CR after Induction-2 received one consolidation cycle and were assigned to alloHSCT. Results: On June 2015, 115 HR ALL pts were evaluable [mean (SD) age 38(13) yr, 67 males, 80/114 precursor B-ALL, 34/114 T-ALL, WBC count 56(96) x109/L]. Results of Induction-1: therapy-related death: 4(4%), resistance: 11 (10%), CR: 95(86%). MRD<0.1% at the end of induction was observed in 75% of CR patients. Induction-2 was administered to 33 patients (no CR: 11, CR and MRD≥0.1%: 22). No differences in the CR rate or in the rate of MRD clearance after induction were observed according to the type of asparaginase administered, although significantly increased hepatic toxicity in consolidation was observed in patients treated with PEG-asparaginase. The 2-yr DFS and OS probabilities for whole series were 51%±18% and 62%±13%. By intention-to treat after Induction-1 36 pts were assigned to alloHSCT and 68 to delayed consolidation and maintenance. The 2-yr DFS and OS probabilities were 54%±25% and 49%±20%, respectively, for pts assigned to alloHSCT, and 50%±22% and 73%±17%, respectively, for those assigned to chemotherapy (P=0.002 for OS comparison). Patients with MRD<0.1% at the end of induction and <0.01% at the end of consolidation (n=51) showed a 2-yr DFS and OS of 55%±25% and 81%±18%, respectively. Conclusions: The preliminary results of this trial, in which the post-induction therapy decision is only based on MRD results, suggest that in HR, Ph-neg adult ALL pts with adequate MRD response after induction and after consolidation the results of therapy are not hampered by avoiding alloHSCT. Supported by grants RD12/0036/0029 (RTICC, FEDER), PI14/01971 FIS, Instituto Carlos III, and SGR225 (GRE), Spain Disclosures No relevant conflicts of interest to declare.

Early Response Characteristics and Blast Cytogenetic FEatures In 5,377 Children with Standard Risk Acute Lymphoblastic Leukemia (SR-ALL): A Children's Oncology Group (COG) Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 414-414
Author(s):  
Kelly W. Maloney ◽  
Mignon L. Loh ◽  
Elizabeth Raetz ◽  
Michael J. Borowitz ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Induction Therapy ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Early Response ◽  
Response To Therapy ◽  
Intrathecal Therapy ◽  
Post Induction

Abstract Abstract 414 The COG uses clinical characteristics, blast cytogenetic features and early response to therapy, as measured by bone marrow (BM) morphology on days 8, 15 and 29 and BM minimal residual disease (MRD) measured by flow cytometry in one of two central COG reference laboratories on day 29 of induction in order to modulate the intensity of post-induction therapy for children with ALL. A slow early response (SER) to therapy was defined by M2/M3 BM on day 15 or MRD ≥ 0.1% on day 29. The COG AALL0331 trial accrued 5377 children with NCI SR- ALL (age 1–10 years with an initial white blood cell count of <50,000/microliter) between 4/11/2005 and 5/28/2010. Induction therapy consisted of dexamethasone (6mg/m2/day × 28 days), PEG asparaginase (2500 units/m2 × 1), vincristine (1.5 mg/m2 weekly × 4) and intrathecal therapy (cytarabine on day 0 and methotrexate on days 8 and 29) according to age based dosing. Those patients with a day 29 M2 BM (5–25% blasts) or MRD ≥1% received two additional weeks of induction therapy using the same agents with one added dose of daunorubicin (25 mg/m2). Children with an M3 marrow (>25% blasts) on day 29, or an M2 marrow or MRD ≥1% on day 43 after 2 weeks of extended induction therapy were classified as induction failures. Following the first month of therapy, patients were assigned to different risk groups for post-induction therapy. We examined the correlations between clinical features, leukemic blast cytogenetic features (favorable: ETV6-RUNX1 and trisomies 4, 10, and 17 or unfavorable: MLL rearrangements, BCR-ABL1 and hypodiploidy), and response to induction therapy. MRD at end induction was ≥ 0.1% more frequently in patients with the absence of either ETV6-RUNX1 (10.4% vs. 3.5%, P<0.0001) or trisomies 4, 10, and 17 (TT) (9.5% vs 5.9%, p=0.0001) or among those who harbored MLL rearrangements (26.1% vs. 8.5%, p=0.0004). MRD > 0.1% at end induction was seen in 23.3% of hypodiploid patients and 32.4% of Philadelphia chromosome + or BCR-ABL1 + patients. In addition, those who had an M2/M3 marrow at day 15 (36.7% vs. 5.9%, p <0.0001) were more likely to have MRD ≥ 0.1% at end induction. There was no difference in the proportion of boys and girls with MRD ≥0.1% (8.5% vs. 8.1%). Only 114/5082 (2.2%) children received extended induction. Induction failures were rare, occurring in only 37/5075 (0.7%) of patients. Induction failures defined by an M3 marrow on day 29 occurred in 6/5123 patients, while induction failures at day 43 after extended induction, occurred in 31/5067 (0.61%) patients (day 43 M2 marrow: 2, day 43 MRD ≥1%: 29). (see Table 1). Conclusions: Inferior MRD responses were associated with the absence of favorable blast cytogenetics and slow initial responses (M2/3 marrow) on day 15 of induction consistent with the known prognostic significance of these variables. Overall, NCI SR patients on AALL0331 had a very low incidence of induction failures, as measured either by bone marrow morphology or by MRD≥1% at day 43. However, the use of MRD identified additional patients who had a suboptimal response to induction, allowing for early augmentation of therapy. Disclosures: Borowitz: genzyme: Research Funding; becton-dickinson: Research Funding; Alexion: Consultancy; beckman-coulter: Research Funding. Mattano:pfizer: Employment.

Clinical utility of terminal deoxynucleotidyl transferase and adenosine deaminase determinations in adult leukemia with a lymphoid phenotype.

1984 ◽  
Vol 2 (8) ◽  
pp. 871-880 ◽  
Author(s):  
E Brusamolino ◽  
P Isernia ◽  
M Lazzarino ◽  
I Scovassi ◽  
U Bertazzoni ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Adenosine Deaminase ◽  
Clinical Utility ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Myelogenous Leukemia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Adult Leukemia

A prospective study was done to assess the clinical utility of terminal deoxynucleotidyl transferase (TdT) and adenosine deaminase (ADA) assays in adult leukemia with a lymphoid phenotype. The study population consisted of 58 patients with adult lymphoblastic leukemia (ALL) at onset, 12 with lymphoblastic lymphoma, 15 with acute unclassifiable leukemia (AUL), and 30 with lymphoid or mixed acute phase of Philadelphia chromosome-positive (Ph' +) chronic myelogenous leukemia (CML). TdT was present in all cases of T-ALL, in 90% of non-T, non-B ALL, and absent in B-ALL; the ADA activity was significantly higher (P less than .01) in T-ALL. TdT was found in 75% of lymphoblastic lymphomas, in 78% of lymphoid, and in 50% of mixed CML transformations; higher ADA activity correlated with TdT positivity in AUL and CML blastic transformations (P less than .001). TdT-positive ALL had a better chance of response to therapy than TdT-negative ALL (P less than 0.01), but survival was not statistically different. TdT was undetectable in the peripheral blood of patients with ALL in complete remission and within the normal range in bone marrow (0.1%-8% of nucleated cells); median ADA activity was as in control subjects. Relapsing ALL patients had TdT and ADA enzymatic activities as before therapy; TdT immunofluorescence test (IF) was positive in 69% of bone marrow and in 100% of CNS relapses. Twenty percent of TdT-positive ALL at onset became TdT-negative in bone marrow at relapse. TdT IF test was instrumental in detecting meningeal leukemia but neither TdT nor ADA could be used as indicators of complete remission or impending relapse because TdT-positive cells were present in normal marrows and wide fluctuations of TdT IF values and of ADA activity were observed in remission.

Factors Associated with Relapse-Free Survival in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Treated with Imatinib-Combined Chemotherapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2813-2813
Author(s):  
Masamitsu Yanada ◽  
Jin Takeuchi ◽  
Isamu Sugiura ◽  
Hideki Akiyama ◽  
Noriko Usui ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
High Dose ◽  
Combined Chemotherapy ◽  
Consolidation Therapy ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Factors Associated

Abstract Imatinib-combined chemotherapy is highly effective for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL); however, a substantial proportion of patients experience relapse. Here, we evaluated 80 patients enrolled in the phase II study by the Japan Adult Leukemia Study Group (JALSG) with extended follow-up with the aim of identifying factors associated with relapse-free survival (RFS). For remission induction therapy, imatinib was administered from day 8 to day 63 in combination with daunorubicin, cyclophosphamide, vincristine (VCR) and prednisolone (PSL). Consolidation therapy consisted of an odd course (C1) comprising high-dose methotrexate (MTX), high-dose cytarabine (Ara-C) and methylprednisolone, and an even course (C2) with single-agent imatinib for 28 days. C1 and C2 were alternated for 4 cycles each. After completion of the consolidation therapy, patients received maintenance therapy consisting of VCR, PSL and imatinib up to 2 years from the date they had attained complete remission (CR). The daily dose of imatinib used in this study was 600 mg. The protocol was reviewed and approved by the institutional review board of each of the participating centers and was conducted in accordance with the Declaration of Helsinki. A total of 80 patients aged between 15 and 63 years were recruited between September 2002 and January 2005. For a median follow-up of 26.7 months (maximum, 52.5 months), 28 of the 77 CR patients showed relapse. Of the 17 relapses observed during the consolidation therapy, 13 occurred during the imatinib course. The probability of RFS was 50.5% at 2 years. Allogeneic transplantation was performed for 60 patients, including 44 in first CR, 12 in second CR, and 12 in non-CR. Neither transcript types nor copy numbers at diagnosis were associated with RFS (p=0.763 and 0.912). Furthermore, RFS for those with an undetectable BCR-ABL level at the end of induction therapy was similar to that for the other CR patients (p=0.707). In contrast, the presence of secondary chromosome aberrations in addition to t(9;22) or variant translocations detected at diagnosis, particularly +der(22)t(9;22) and abn(9p), was significantly associated with inferior RFS (p=0.003). Multivariate analysis revealed that the presence of additional chromosome aberrations was the only significant prognostic factor for RFS (HR, 2.84; 95% CI, 1.12–7.19; p=0.027). Even after allogeneic HSCT, patients with additional aberrations appeared to have a trend for shorter RFS than those without (p=0.080), but this might reflect a larger proportion of transplantation beyond first CR in the former (31% vs 17%). Although these results need to be validated in the context of the ABL kinase domain mutations, our findings may be of clinical importance for the future treatment of Ph+ ALL.

Philadelphia chromosome and terminal transferase-positive acute leukemia: similarity of terminal phase of chronic myelogenous leukemia and de novo acute presentation.

1983 ◽  
Vol 1 (11) ◽  
pp. 669-676 ◽  
Author(s):  
K Jain ◽  
Z Arlin ◽  
R Mertelsmann ◽  
T Gee ◽  
S Kempin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Chronic Myelogenous Leukemia ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Leukocyte Antigen ◽  
Terminal Transferase

Twenty-eight patients with Philadelphia chromosome (Ph1)--positive and terminal transferase (TdT)--positive acute leukemia (AL) were treated with intensive chemotherapy used for adult acute lymphoblastic leukemia (L-10 and L-10M protocols). Fifteen patients had a documented chronic phase of Ph1-positive chronic myelogenous leukemia preceding the acute transformation (TdT + BLCML) while the remaining 13 patients did not (TdT + Ph1 + AL). An overall complete remission (CR) rate of 71% was obtained with a median survival of 13 months in the responders. Clinical presentation, laboratory data, cytogenetics, response to treatment, and survivals of the two groups of patients are compared. These results appear to be similar, suggesting a common or closely related origin. Since the overall survival of those receiving chemotherapy maintenance is poor, three patients underwent allogeneic bone marrow transplantation (BMT) from histocompatibility leukocyte antigen--matched siblings after they achieved CR. One of them is a long-term survivor (35 + months) with a Ph1-negative bone marrow. New techniques such as BMT should be considered in young patients with a histocompatibility leukocyte antigen--compatible sibling once a CR has been achieved.

scholarly journals Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group

Blood ◽  
2008 ◽  
Vol 111 (6) ◽  
pp. 2984-2990 ◽  
Author(s):  
Stella M. Davies ◽  
Michael J. Borowitz ◽  
Gary L. Rosner ◽  
Kristin Ritz ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Response To Therapy ◽  
Oncology Group ◽  
Risk Status ◽  
Prognostic Features ◽  
Minimal Residual

Abstract Minimal residual disease (MRD) as a marker of antileukemic drug efficacy is being used to assess risk status and, in some cases, to adjust the intensity of therapy. Within known prognostic categories, the determinants of MRD are not known. We measured MRD by flow cytometry at day 8 (in blood) and at day 28 (in bone marrow) of induction therapy in more than 1000 children enrolled in Pediatric Oncology Group therapy protocols 9904, 9905, and 9906. We classified patients as “best risk” if they had cleared MRD by day 8 of therapy and as “worst risk” if they had MRD remaining in bone marrow at day 28, and tested whether MRD was related to polymorphisms in 16 loci in genes hypothesized to influence response to therapy in acute lymphoblastic leukemia (ALL). After adjusting for known prognostic features such as presence of the TEL-AML1 rearrangement, National Cancer Institute (NCI) risk status, ploidy, and race, the G allele of a common polymorphism in chemokine receptor 5 (CCR5) was associated with more favorable MRD status than the A allele (P = .009, logistic regression), when comparing “best” and “worst” risk groups. These data are consistent with growing evidence that both acquired and host genetics influence response to cancer therapy.

scholarly journals High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia

2013 ◽  
Vol 31 (6) ◽  
pp. 676-683 ◽  
Author(s):  
Susan O'Brien ◽  
Gary Schiller ◽  
John Lister ◽  
Lloyd Damon ◽  
Stuart Goldberg ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Chemotherapy Resistance ◽  
High Dose ◽  
Rapid Progression ◽  
Target Tissue ◽  
Vincristine Sulfate ◽  
Pivotal Phase

Purpose Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) –negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT). Patients and Methods Sixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m2, without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi). Results The CR/CRi rate was 20% and overall response rate was 35%. VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%). Conclusion High-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR.

Outcome of Allogeneic Hematopoietic Stem-Cell Transplantation in Adult Patients With Acute Lymphoblastic Leukemia: No Difference in Related Compared With Unrelated Transplant in First Complete Remission

2004 ◽  
Vol 22 (14) ◽  
pp. 2816-2825 ◽  
Author(s):  
Michael G. Kiehl ◽  
Ludwig Kraut ◽  
Rainer Schwerdtfeger ◽  
Bernd Hertenstein ◽  
Mats Remberger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Hematopoietic Stem ◽  
First Complete Remission

Purpose The role of unrelated allogeneic stem-cell transplantation in acute lymphoblastic leukemia (ALL) patients is still not clear, and only limited data are available from the literature. We analyzed factors affecting clinical outcome of ALL patients receiving a related or unrelated stem-cell graft from matched donors. Patients and Methods The total study population was 264 adult patients receiving a myeloablative allogeneic stem-cell transplant for ALL at nine bone marrow transplantation centers between 1990 and 2002. Of these, 221 patients receiving a matched related or unrelated graft were analyzed. One hundred forty-eight patients received transplantation in complete remission; 62 patients were in relapse; and 11 patients were refractory to chemotherapy before transplant. Fifty percent of patients received bone marrow, and 50% received peripheral blood stem cell from a human leukocyte antigen–identical related (n = 103), or matched unrelated (n = 118) donor. Results Disease-free survival (DFS) at 5 years was 28%, with 76 patients (34%) still alive (2.2 to 103 months post-transplantation), and 145 deceased (65 relapses, transplant-related mortality, 45%). We observed an advantage regarding DFS in favor of patients receiving transplantation during their first complete remission (CR) in comparison with patients receiving transplantation in or after second CR (P = .014) or who relapsed (P < .001). We observed a clear trend toward improved survival in favor of B-lineage ALL patients compared with T-lineage ALL patients (P = .052), and Philadelphia chromosome–positive patients had no poorer outcome than Philadelphia chromosome–negative patients. Total-body irradiation–based conditioning improved DFS in comparison with busulfan (P = .041). Conclusion Myeloablative matched related or matched unrelated allogeneic hematopoietic stem-cell transplantation in ALL patients should be performed in first CR.

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