scholarly journals Prognostic value of low-level MRD in adult acute lymphoblastic leukemia detected by low- and high-throughput methods

2022 ◽  
Author(s):  
Michaela Kotrova ◽  
Johannes Koopmann ◽  
Heiko Trautmann ◽  
Nael Alakel ◽  
Joachim Beck ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Molecular Response ◽  
Immune Gene ◽  
Assay Sensitivity ◽  
Group Assignment ◽  
Fitting In ◽  
Complete Molecular Response

Persistence of minimal residual disease (MRD) after induction/consolidation therapy in acute lymphoblastic leukemia is the leading cause of relapse. The GMALL 07/2003 study used MRD detection by RQ-PCR of clonal immune gene rearrangements with 1x10-4 as discriminating cut-off: levels ≥1x10-4 define molecular failure and MRD-negativity with an assay sensitivity of at least 1x10-4 defines complete molecular response. The clinical relevance of MRD results not fitting in these categories is unclear and termed "molecular not evaluable" (MolNE) towards MRD-based treatment decisions. Within the GMALL 07/03 study, 1019 consecutive bone marrow samples after first consolidation were evaluated for MRD. Patients with complete molecular response had significantly better outcome (five-year overall survival, 5y-OS=85±2%, n=603; five-year disease-free survival, 5y-DFS=73±2%, n=599) compared to patients with molecular failure 5y-OS=40±3%, n=238; 5y-DFS=29±3%, n=208), with MolNE patients in-between (5y-OS=66±4%, 5y-DFS=52±4%, n=178). Of MolNE samples re-analyzed using next-generation sequencing (NGS), patients with undetectable NGS-MRD (n=44; 5y-OS=88±5%, 5y-DFS=70±7%) had significantly better outcome than those with positive NGS-MRD (n=42; 5y-OS=37±8%, 5y-DFS=33±8%). MolNE MRD results are not just borderline values with questionable relevance, but form an intermediate risk group, assignment of which can be further improved by NGS.

Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)

Blood ◽  
2005 ◽  
Vol 106 (2) ◽  
pp. 458-463 ◽  
Author(s):  
Barbara Wassmann ◽  
Heike Pfeifer ◽  
Michael Stadler ◽  
Martin Bornhaüser ◽  
Gesine Bug ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Disease Free Survival ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
Free Survival ◽  
High Relapse Rate ◽  
Polymerase Chain

Abstract In adult Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL), minimal residual disease (MRD) after stem cell transplantation (SCT) is associated with a relapse probability exceeding 90%. Starting imatinib in the setting of MRD may decrease this high relapse rate. In this prospective multicenter study, 27 Ph+ ALL patients received imatinib upon detection of MRD after SCT. Bcr-abl transcripts became undetectable in 14 (52%) of 27 patients, after a median of 1.5 months (0.9-3.7 months) (earlyCRmol). All patients who achieved an earlyCRmol remained in remission for the duration of imatinib treatment; 3 patients relapsed after imatinib was discontinued. Failure to achieve polymerase chain reaction (PCR) negativity shortly after starting imatinib predicted relapse, which occurred in 12 (92%) of 13 patients after a median of 3 months. Disease-free survival (DFS) in earlyCRmol patients is 91% ± 9% and 54% ± 21% after 12 and 24 months, respectively, compared with 8% ± 7% after 12 months in patients remaining MRD+ (P < .001). In conclusion, approximately half of patients with Ph+ ALL receiving imatinib for MRD positivity after SCT experience prolonged DFS, which can be anticipated by the rapid achievement of a molecular complete remission (CR). Continued detection of bcr-abl transcripts after 2 to 3 months on imatinib identifies patients who will ultimately experience relapse and in whom additional or alternative antileukemic treatment should be initiated.

scholarly journals Outcomes after late bone marrow and very early central nervous system relapse of childhood B-acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433

Haematologica ◽  
2020 ◽  
Vol 106 (1) ◽  
pp. 46-55 ◽  
Author(s):  
Glen Lew ◽  
Yichen Chen ◽  
Xiaomin Lu ◽  
Susan R. Rheingold ◽  
James A. Whitlock ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Central Nervous System Relapse ◽  
Oncology Group

Outcomes after relapse of childhood B-acute lymphoblastic leukemia (B-ALL) are poor, and optimal therapy is unclear. Children’s Oncology Group study AALL0433 evaluated a new platform for relapsed ALL. Between March 2007 and October 2013 AALL0433 enrolled 275 participants with late bone marrow or very early isolated central nervous system (iCNS) relapse of childhood B-ALL. Patients were randomized to receive standard versus intensive vincristine dosing; this randomization closed due to excess peripheral neuropathy in 2010. Patients with matched sibling donors received allogeneic hematopoietic cell transplantation (HCT) after the first three blocks of therapy. The prognostic value of minimal residual disease (MRD) was also evaluated in this study. The 3-year event free and overall survival (EFS/OS) for the 271 eligible patients were 63.6% +/- 3.0% and 72.3% +/- 2.8% respectively. MRD at the end of Induction-1 was highly predictive of outcome, with 3-year EFS/OS of 84.9 +/- 4.0% and 93.8 +/- 2.7% for patients with MRD <0.1%, vs. 53.7 +/- 7.8% and 60.6 +/- 7.8% for patients with MRD ≥0.1% (p<0.0001). Patients who received HCT vs. chemotherapy alone had an improved 3-year disease-free survival (77.5 +/- 6.2% vs. 66.9 +/- 4.5%, p=0.03) but not OS (81.5 +/- 5.8% for HCT vs. 85.8 +/- 3.4% for chemotherapy, p=0.46). Patients with early iCNS relapse fared poorly, with a 3-year EFS/OS of 41.4% +/- 9.2% and 51.7% +/- 9.3%, respectively. Infectious toxicities of the chemotherapy platform were significant. The AALL0433 chemotherapy platform is efficacious for late bone marrow relapse of B-ALL, but with significant toxicities. The MRD threshold of 0.1% at the end of Induction-1 was highly predictive of outcome. The optimal role for HCT for this patient population remains uncertain. This trial is registered at clinicaltrials.gov (NCT# 00381680).

scholarly journals Outcome of Children With Hypodiploid Acute Lymphoblastic Leukemia: A Retrospective Multinational Study

2019 ◽  
Vol 37 (10) ◽  
pp. 770-779 ◽  
Author(s):  
Ching-Hon Pui ◽  
Paola Rebora ◽  
Martin Schrappe ◽  
Andishe Attarbaschi ◽  
Andre Baruchel ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Survival Rate ◽  
Hematopoietic Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Remission Induction ◽  
Event Free Survival ◽  
Free Survival

PURPOSE We determined the prognostic factors and utility of allogeneic hematopoietic cell transplantation among children with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL) treated in contemporary clinical trials. PATIENTS AND METHODS This retrospective study collected data on 306 patients with hypodiploid ALL who were enrolled in the protocols of 16 cooperative study groups or institutions between 1997 and 2013. The clinical and biologic characteristics, early therapeutic responses as determined by minimal residual disease (MRD) assessment, treatment with or without MRD-stratified protocols, and allogeneic transplantation were analyzed for their impact on outcome. RESULTS With a median follow-up of 6.6 years, the 5-year event-free survival rate was 55.1% (95% CI, 49.3% to 61.5%), and the 5-year overall survival rate was 61.2% (95% CI, 55.5% to 67.4%) for the 272 evaluable patients. Negative MRD at the end of remission induction, high hypodiploidy with 44 chromosomes, and treatment in MRD-stratified protocols were associated with a favorable prognosis, with a 5-year event-free survival rate of 75% (95% CI, 66.0% to 85.0%), 74% (95% CI, 61.0% to 89.0%), and 62% (95% CI, 55.0% to 69.0%), respectively. After exclusion of patients with high hypodiploidy with 44 chromosomes and adjustment for waiting time to transplantation and for covariables in a Poisson model, disease-free survival did not differ significantly ( P = .16) between the 42 patients who underwent transplantation and the 186 patients who received chemotherapy only, with an estimated 5-year survival rate of 59% (95% CI, 46.5% to 75.0%) versus 51.5% (95% CI, 44.7% to 59.4%), respectively. Transplantation produced no significant impact on outcome compared with chemotherapy alone, especially among the subgroup of patients who achieved a negative MRD status upon completion of remission induction. CONCLUSION MRD-stratified treatments improved the outcome for children with hypodiploid ALL. Allogeneic transplantation did not significantly improve outcome overall and, in particular, for patients who achieved MRD-negative status after induction.

scholarly journals Induction of Effector and Memory Cellular Immunity in a Patient with Long-Term Complete Molecular Response to Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

2020 ◽  
Vol 13 (2) ◽  
pp. 990-996
Author(s):  
Tatsuro Jo ◽  
Haruna Shioya ◽  
Hiroo Tominaga ◽  
Takahiro Sakai ◽  
Shizuka Hayashi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Molecular Response ◽  
Gene Repertoire ◽  
Monosomy 7 ◽  
Long Time ◽  
Lineage Markers ◽  
Complete Molecular Response

This case report is about a patient who suffered from Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia. The blasts were positive for myeloid-lineage markers including CD13 and CD33, as well as B-cell-lineage markers. Minor bcr-abl1 mRNA was detected by real-time quantitative polymerase chain reaction. Chromosomal abnormality monosomy 7 was also observed, in addition to Ph1. Despite treatment difficulties that were anticipated based on these findings, the patient had long-time complete molecular response (CMR) for approximately 5 years using chemotherapy and two tyrosine kinase inhibitors, imatinib and dasatinib. Lymphocytes were elevated after the patient switched from imatinib to dasatinib, and a T-cell receptor (TCR) V beta gene repertoire analysis revealed oligoclonal expansion of effector and memory cytotoxic T lymphocytes (CTLs), including Wilms tumor 1-specific CTLs. More specifically, the two memory CTLs expressing TCR V beta 3 and V beta 7.1 gradually increased after dasatinib administration. The activation and maintenance of anti-leukemia immunity may have allowed the patient to obtain long-time CMR. These results highlight that obtaining memory CTLs for leukemia cells may lead to safe withdrawal from dasatinib in the patient.

scholarly journals Blinatumomab + Ponatinib for Relapsed Ph1-Positive Acute Lymphoblastic Leukemia: The French Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4014-4014 ◽  
Author(s):  
Marie-Anne Couturier ◽  
Xavier Thomas ◽  
Francoise Huguet ◽  
Céline Berthon ◽  
Célestine Simand ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Philadelphia Chromosome ◽  
New Drugs ◽  
Molecular Response ◽  
Complete Molecular Response

Abstract Prognosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1+ ALL) has been considerably improved since the beginning of the BCR-ABL1 tyrosine kinase inhibitors (TKI) era 20 years ago. However, the prognosis of patients with a refractory/relapsed (including molecular relapse) disease is still very dismal. New drugs or combination of new drugs may improve outcomes of these patients. For example, ponatinib, a 3rd-generation oral TKI, known to have activity against BCR-ABL1 T315I mutations, has shown some efficacy in this context. Similarly, a recent study has reported very encouraging results of the bispecific anti-CD3/CD19 monoclonal antibody blinatumomab as single-agent in refractory/relapsed Ph1+ ALL. Data regarding the efficacy and tolerance of a combination of blinatumomab+ponatinib (blina/pona) are still scarce. This was a retrospective study with the aim to report outcomes of patients receiving a combination of blina/pona for refractory/relapsed Ph1+ ALL in France. Fifteen adults from 8 French centers were identified and data were collected by physicians of each centers, then gathered for the purpose of this study. There were 9 males and 6 females, with a median age of 53 years (range:17-72). All patients, but 2 with blast crisis of chronic myeloid leukemia, had de novo Ph1+ ALL. Four cases had BCR-ABL1 T315I mutation. Patients received the blina/pona combination, either after a first (n=8) or a second (n=7) cytologic relapse. There was no refractory patient in theses series. Previous allograft and autograft has been performed in 7 and 2 patients, respectively. The majority of patients (n=12) had previously received 2 or more lines of TKI. The median time between the first cycle of blina/pona and diagnosis was 14 months (range: 8-40). The median number of blinatumomab cycle (28 mg/day by continuous infusion for 28 days every 6 weeks) administered per patient was 3 (range: 1-6) while ponatinib was concomittantly administered continuously at an initial dose of 45 mg once daily in 11 pts (73%) and 30 mg in 4 pts (27%). Median duration of ponatinib administration was 4 months (range: 1.1-10.9) from first blinatumomab cycle. The toxicity profile was safe: all patients received a complete first cycle without grade 3-4 adverse events. After cycle 1, blinatumomab was stopped in 47% of cases because of neurologic events in 4 and infections in 3; ponatinib was stopped in 33% of cases because of neurologic events in 3, fluid retention in 1 and severe arteriopathy in 1 patient with other vascular disease risk factors. All neurologic events resolved after stopping blinatumomab or ponatinib. The majority of patients were evaluated after one cycle (n=11, after cycle 2 n=3, after cycle 3 n=1). All but one patients (93%) obtained a cytologic complete remission (CR), of whom 12/14 (86%) achieved a complete molecular response. However, 2 patients were documented with CNS relapse at the time of blina/pona evaluation although in bone marrow molecular remission. Both obtained clearance of leukemic blasts after intrathecal infusion of chemotherapy. Then, 5 patients underwent allogeneic transplant (including 2 patients already allotransplanted before blina/pona) and 1 patient received donor lymphocyte infusion. Seven cases pursued maintenance therapy with ponatinib as single agent after stopping blinatumomab. With a median follow-up of 8 months (range: 2.6-30.2) for alive patients, median overall and leukemia-free survivals from first cycle of blina/pona were 8.5 months (range: 1.7-30.2) and 8 months (range: 1.3-30.2), respectively. At last follow-up (July 2018), only 4 relapses had occurred at a median of 3.3 months (range: 1.3-8.3) from first blina/pona cycle and 6 patients had died (3 bacterial infections, 1 fungal infection, 1 secondary cancer and 1 ALL relapse). All alive patients (n=9) but one (cytologic CR but detectable minimal residual disease) are in complete molecular response. Four patients are still under ponatinib medication at last follow-up. The combination of blinatumomab+ponatinib appears effective and tolerable in relapsed Ph1+ALL patients and may replace chemotherapy salvage regimens. The combination should be tested in first-line therapy in the future. Our results have also to be confirmed prospectively on a larger cohort of patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol

2021 ◽  
pp. JCO.20.02333
Author(s):  
Janine Stutterheim ◽  
Inge M. van der Sluis ◽  
Paola de Lorenzo ◽  
Julia Alten ◽  
Philip Ancliffe ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Cell Receptor ◽  
Treatment Interventions ◽  
T Cell Receptor Genes ◽  
High Incidence ◽  
Minimal Residual

PURPOSE Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide). MATERIALS AND METHODS MRD was measured in 249 infants by DNA-based polymerase chain reaction of rearranged KMT2A, immunoglobulin, and/or T-cell receptor genes, at the end of induction (EOI) and end of consolidation (EOC). MRD results were classified as negative, intermediate (< 5 × 10−4), and high (≥ 5 × 10−4). RESULTS EOI MRD levels predicted outcome with 6-year disease-free survival (DFS) of 60.2% (95% CI, 43.2 to 73.6), 45.0% (95% CI, 28.3 to 53.1), and 33.8% (95% CI, 23.8 to 44.1) for infants with negative, intermediate, and high EOI MRD levels, respectively ( P = .0039). EOC MRD levels were also predictive of outcome, with 6-year DFS of 68.2% (95% CI, 55.2 to 78.1), 40.1% (95% CI, 28.1 to 51.9), and 11.9% (95% CI, 2.6 to 29.1) for infants with negative, intermediate, and high EOC MRD levels, respectively ( P < .0001). Analysis of EOI MRD according to the type of consolidation treatment showed that infants treated with lymphoid-style consolidation had 6-year DFS of 78.2% (95% CI, 51.4 to 91.3), 47.2% (95% CI, 33.0 to 60.1), and 23.2% (95% CI, 12.1 to 36.4) for negative, intermediate, and high MRD levels, respectively ( P < .0001), while for myeloid-style–treated patients the corresponding figures were 45.0% (95% CI, 23.9 to 64.1), 41.3% (95% CI, 23.2 to 58.5), and 45.9% (95% CI, 29.4 to 60.9). CONCLUSION This study provides support for the idea that induction therapy selects patients for subsequent therapy; infants with high EOI MRD may benefit from AML-like consolidation (DFS 45.9% v 23.2%), whereas patients with low EOI MRD may benefit from ALL-like consolidation (DFS 78.2% v 45.0%). Patients with positive EOC MRD had dismal outcomes. These findings will be used for treatment interventions in the next Interfant protocol.

Rapid molecular response during early induction chemotherapy predicts a good outcome in childhood acute lymphoblastic leukemia

Blood ◽  
2000 ◽  
Vol 95 (3) ◽  
pp. 790-794 ◽  
Author(s):  
E. Renate Panzer-Grümayer ◽  
Monika Schneider ◽  
Simon Panzer ◽  
Karin Fasching ◽  
Helmut Gadner
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Risk Stratification ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Response To Therapy ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Induction Treatment ◽  
Molecular Response ◽  
Significant Difference

Early response to therapy is an independent prognostic factor in childhood acute lymphoblastic leukemia. Although most patients have rapid early responses, as detected by morphology, 15% to 20% of patients have relapses. The authors evaluated residual disease by molecular methods on day 15 of minimal residual disease (MRD) therapy and compared these data with their recently established MRD-based risk stratification, defined by MRD levels 5 weeks after induction treatment and before consolidation. All 68 children treated according to current Berlin-Frankfurt-Münster (BFM) protocols went into morphologically complete remission after induction. There was a significant difference in outcome between children with rapid disease clearance and those with high levels of day-15 MRD (P = .035). Among patients with high levels of day-15 MRD, only the MRD-based risk stratification was predictive of the outcome. All patients with negative or low day-15 MRD had excellent prognoses and were in the MRD-based low-risk group. Thus, after only 2 weeks of treatment, the authors were able to identify a patient population of 20% who may benefit from the least intensive treatment.

scholarly journals Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction

2001 ◽  
Vol 119 (5) ◽  
pp. 175-180 ◽  
Author(s):  
Carlos Alberto Scrideli ◽  
Ricardo Defavery ◽  
José Eduardo Bernardes ◽  
Luíz Gonzaga Tone
Keyword(s):  
Polymerase Chain Reaction ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Chain Reaction ◽  
Significant Difference ◽  
Polymerase Chain ◽  
Minimal Residual

CONTEXT: The CDR-3 region of heavy-chain immunoglobulin has been used as a clonal marker in the study of minimal residual disease in children with acute lymphoblastic leukemia. Southern blot and polymerase chain reaction studies have demonstrated the occurrence of bi/oligoclonality in a variable number of cases of B-lineage acute lymphoblastic leukemia, a fact that may strongly interfere with the detection of minimal residual disease. Oligoclonality has also been associated with a poorer prognosis and a higher chance of relapse. OBJECTIVES: To correlate bi/oligoclonality, detected by polymerase chain reaction in Brazilian children with B-lineage acute lymphoblastic leukemia with a chance of relapse, with immunophenotype, risk group, and disease-free survival. DESIGN: Prospective study of patients’ outcome. SETTING: Pediatric Oncology Unit of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. PARTICIPANTS: 47 children with acute lymphoblastic leukemia DIAGNOSTIC TEST: Polymerase chain reaction using consensus primers for the CDR-3 region of heavy chain immunoglobulin (FR3A, LJH and VLJH) for the detection of clonality. RESULTS: Bi/oligoclonality was detected in 15 patients (31.9%). There was no significant difference between the groups with monoclonality and biclonality in terms of the occurrence of a relapse (28.1% versus 26.1%), presence of CALLA+ (81.2% versus 80%) or risk group (62.5% versus 60%). Disease-free survival was similar in both groups, with no significant difference (p: 0.7695). CONCLUSIONS: We conclude that bi/oligoclonality was not associated with the factors investigated in the present study and that its detection in 31.9% of the patients may be important for the study and monitoring of minimal residual disease.

Minimal Residual Disease Tests Provide an Independent Predictor of Clinical Outcome in Adult Acute Lymphoblastic Leukemia

2002 ◽  
Vol 20 (4) ◽  
pp. 1094-1104 ◽  
Author(s):  
Forida Y. Mortuza ◽  
Mary Papaioannou ◽  
Ilidia M. Moreira ◽  
Luke A. Coyle ◽  
Paula Gameiro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Clinical Outcome ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Adult Patients ◽  
Exact Test ◽  
Minimal Residual

PURPOSE: Investigation of minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) using molecular markers has proven superior to other standard criteria (age, sex, and WBC) in distinguishing patients at high, intermediate, and low risk of relapse. The aim of our study was to determine whether MRD investigation is valuable in predicting outcome in Philadelphia-negative adult patients with ALL. PATIENTS AND METHODS: MRD was assessed in 85 adult patients with B-lineage ALL by semiquantitative immunoglobulin H gene analysis on bone marrow samples collected during four time bands in the first 24 months of treatment. Fifty patients received chemotherapy only and 35 patients received allogeneic (n = 19) or autologous (n = 16) bone marrow transplantation (BMT) in first clinical remission. The relationship between MRD status and clinical outcome was investigated and compared with age, sex, immunophenotype, and presenting WBC count. RESULTS: Fisher’s exact test established a statistically significant concordance between MRD results and clinical outcome at all times. Disease-free survival (DFS) rates for MRD-positive and -negative patients and log-rank testing established that MRD positivity was associated with increased relapse rates at all times (P < .05) but was most significant at 3 to 5 months after induction and beyond. MRD status after allogeneic BMT rather than before was found to be an important predictor of outcome in 19 adult patients with ALL tested. In patients receiving autologous BMT (n = 16), the MRD status before BMT was more significant (P = .005). CONCLUSION: The association of MRD test results and DFS was independent of and greater than other standard predictors of outcome and is therefore important in determining treatment for individual patients.

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