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 Myeloablative Cord Blood Transplantation Yields Excellent Disease Free Survival in Patients with Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4693-4693
Author(s):  
David Charles Keahi Oliver ◽  
Ryan D Cassaday ◽  
Ralph P Ermoian ◽  
Ann Dahlberg ◽  
Colleen Delaney ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cumulative Incidence ◽  
Hematopoietic Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cord Blood Transplantation ◽  
Disease Free Survival ◽  
Free Survival ◽  
Blood Transplantation ◽  
Disease Free

Abstract Background: Allogeneic hematopoietic cell transplantation (HCT) is a potential curative treatment for children and adults with acute lymphoblastic leukemia (ALL). However, relapse occurs in approximately 30% of patients with ALL after HCT, with even worse outcomes in patients with minimal residual disease (MRD) pre-transplant [1]. Lower relapse rates have been reported for patients undergoing cord blood transplantation (CBT) compared to unrelated donor transplant. In the present study we sought not only to evaluate outcomes for ALL patients undergoing a myeloablative CBT, but also to see if the outcomes varied according to MRD status. Methods: Using prospectively collected data, we reviewed 67 consecutive patients with ALL who received a CBT between 2006 and 2016. The conditioning regimens consisted of either TBI (1320 cGy), Cytoxan and Fludarabine (FLU), (n=49) or Treosulfan (Treo), FLU and 200 cGY TBI (n=18). GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil (MMF). Donor units were selected to be at least a 4 out of 6 match to recipient at HLA-A and HLA-B antigens and HLA-DRB allele. Ten-color multiparameter flow cytometry studies on bone marrow aspirates were performed before HCT to determine the presence of MRD. Disease free-survival (DFS) was evaluated using the method of Kaplan and Meier. Probabilities of non-relapse mortality (NRM) and relapse were summarized using cumulative incidence estimates using the appropriate competing risks. Results: Patient characteristics are shown in Table 1. The median age and weight was 22 years (range, 0.6-58 years) and 57 kg (range 8-99 kg), respectively. Thirty-nine patients (58%) were non-Caucasian. At the time of transplant 32 patients (47%) were in first complete remission (CR1), 28 (42%) in CR2 and 7 (11%) in CR≥3. Any level of residual disease was considered MRD-positive (n=22). Fifteen patients (22%) had Ph+ ALL. Nine patients (13%) had a prior allogeneic transplant. The majority of patients (n=48; 72%) received a double-CB graft; the rest received a single-CB graft. In addition, 14 patients (21%) received an ex-vivo-expanded CB unit as part of their graft, combined with an unmanipulated CB unit. Median time to engraftment was 31 days (range, 21-80 days). The overall DFS at 5 years was 74% (CI 95%: 60-83) with no difference between MRD-negative 78% (CI 95%: 61-88) and MRD-positive patients 67% (CI 95%:43-81) (p=0.40) [Figure 1A and 1B]. The overall cumulative incidence of relapse and NRM at 5 years post-transplant was 14% (CI 95%: 5-31) and 12% (95%: 3-26), respectively. The risk of relapse was not significantly higher in MRD-positive compared to MRD-negative (HR 1.80 (95 CI: 0.50-6.51) p=0.36), when adjusting for year of transplant, CMV serostatus, age, and disease risk. The cumulative incidence of acute GVHD grade II-IV and III-IV at day 100 was 86% (CI 95%: 75-92) and 16% (CI 95%: 8-26), respectively. Conclusions: Our data suggest that outcomes in patients with ALL following myeloablative CBT are remarkable with 74% DFS at 5 years and very low rate of relapse. The implication of these results is particularly important for patients from racial and ethnic minorities. Indeed, because mismatches in CB units can be tolerated, it is possible to find suitable donors for nearly all patients, regardless of their race/ethnicity. Furthermore, the risk of relapse was similar between MRD-negative and positive patients, although this requires further study in larger populations given the relatively low number of MRD-positive patients. References: 1. Bar M, Wood BL, Radich JP et al. Impact of minimal residual disease, detected by flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia. Leuk Res Treatment. 2014;2014:421723 Disclosures Delaney: Nohla Therapeutics: Employment.

scholarly journals Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2814-2822 ◽  
Author(s):  
CA Linker ◽  
LJ Levitt ◽  
M O'Donnell ◽  
SJ Forman ◽  
CA Ries
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Cell Phenotype ◽  
Free Survival ◽  
Prognostic Features ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Disease Free

Abstract We treated 109 patients with adult acute lymphoblastic leukemia (ALL) diagnosed by histochemical and immunologic techniques. Patients were excluded only for age greater than 50 years and Burkitt's leukemia. Treatment included a four-drug remission induction phase followed by alternating cycles of noncrossresistant chemotherapy and prolonged oral maintenance therapy. Eighty-eight percent of patients entered complete remission. With a median follow-up of 77 months (range, 48 to 111 months), 42% +/- 6% (SEM) of patients achieving remission are projected to remain disease-free at 5 years, and disease-free survival for all patients entered on study is 35% +/- 5%. Failure to achieve remission within the first 4 weeks of therapy and the presence of the Philadelphia chromosome are associated with a 100% risk of relapse. Remission patients with neither of these adverse features have a 48% +/- 6% probability of remaining in continuous remission for 5 years. Patients with T-cell phenotype have a favorable prognosis with 59% +/- 13% of patients achieving remission remaining disease-free compared with 31% +/- 7% of CALLA-positive patients. Intensive chemotherapy may produce prolonged disease-free survival in a sizable fraction of adults with ALL. Improved therapy is needed, especially for patients with adverse prognostic features.

scholarly journals Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2814-2822 ◽  
Author(s):  
CA Linker ◽  
LJ Levitt ◽  
M O'Donnell ◽  
SJ Forman ◽  
CA Ries
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Cell Phenotype ◽  
Free Survival ◽  
Prognostic Features ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Disease Free

We treated 109 patients with adult acute lymphoblastic leukemia (ALL) diagnosed by histochemical and immunologic techniques. Patients were excluded only for age greater than 50 years and Burkitt's leukemia. Treatment included a four-drug remission induction phase followed by alternating cycles of noncrossresistant chemotherapy and prolonged oral maintenance therapy. Eighty-eight percent of patients entered complete remission. With a median follow-up of 77 months (range, 48 to 111 months), 42% +/- 6% (SEM) of patients achieving remission are projected to remain disease-free at 5 years, and disease-free survival for all patients entered on study is 35% +/- 5%. Failure to achieve remission within the first 4 weeks of therapy and the presence of the Philadelphia chromosome are associated with a 100% risk of relapse. Remission patients with neither of these adverse features have a 48% +/- 6% probability of remaining in continuous remission for 5 years. Patients with T-cell phenotype have a favorable prognosis with 59% +/- 13% of patients achieving remission remaining disease-free compared with 31% +/- 7% of CALLA-positive patients. Intensive chemotherapy may produce prolonged disease-free survival in a sizable fraction of adults with ALL. Improved therapy is needed, especially for patients with adverse prognostic features.

scholarly journals IKZF1plus Defines a New Minimal Residual Disease–Dependent Very-Poor Prognostic Profile in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia

2018 ◽  
Vol 36 (12) ◽  
pp. 1240-1249 ◽  
Author(s):  
Martin Stanulla ◽  
Elif Dagdan ◽  
Marketa Zaliova ◽  
Anja Möricke ◽  
Chiara Palmi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Cell Precursor ◽  
Free Survival ◽  
Prognostic Profile ◽  
Minimal Residual

Purpose Somatic deletions that affect the lymphoid transcription factor–coding gene IKZF1 have previously been reported as independently associated with a poor prognosis in pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). We have now refined the prognostic strength of IKZF1 deletions by analyzing the effect of co-occurring deletions. Patients and Methods The analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica–Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22.33/Yp11.31 (PAR1 region; CRLF2, CSF2RA, and IL3RA), and ERG; replication of findings involved 417 patients from the same trial. Results IKZF1 deletions that co-occurred with deletions in CDKN2A, CDKN2B, PAX5, or PAR1 in the absence of ERG deletion conferred the worst outcome and, consequently, were grouped as IKZF1plus. The IKZF1plus group comprised 6% of patients with BCP ALL, with a 5-year event-free survival of 53 ± 6% compared with 79 ± 5% in patients with IKZF1 deletion who did not fulfill the IKZF1plus definition and 87 ± 1% in patients who lacked an IKZF1 deletion ( P ≤ .001). Respective 5-year cumulative relapse incidence rates were 44 ± 6%, 11 ± 4%, and 10 ± 1% ( P ≤ .001). Results were confirmed in the replication cohort, and multivariable analyses demonstrated independence of IKZF1plus. The IKZF1plus prognostic effect differed dramatically in analyses stratified by minimal residual disease (MRD) levels after induction treatment: 5-year event-free survival for MRD standard-risk IKZF1plus patients was 94 ± 5% versus 40 ± 10% in MRD intermediate- and 30 ± 14% in high-risk IKZF1plus patients ( P ≤ .001). Corresponding 5-year cumulative incidence of relapse rates were 6 ± 6%, 60 ± 10%, and 60 ± 17% ( P ≤ .001). Conclusion IKZF1plus describes a new MRD-dependent very-poor prognostic profile in BCP ALL. Because current AIEOP-BFM treatment is largely ineffective for MRD-positive IKZF1plus patients, new experimental treatment approaches will be evaluated in our upcoming trial AIEOP-BFM ALL 2017.

scholarly journals Validation of Minimal Residual Disease as Surrogate Endpoint for Event-Free Survival in Childhood Acute Lymphoblastic Leukemia

2018 ◽  
Vol 2 (4) ◽  
Author(s):  
Stefania Galimberti ◽  
Meenakshi Devidas ◽  
Ausiliatrice Lucenti ◽  
Giovanni Cazzaniga ◽  
Anja Möricke ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Surrogate Endpoint ◽  
Phase Iii ◽  
Event Free Survival ◽  
Free Survival ◽  
The Individual ◽  
Minimal Residual

Abstract Background The aim of this study was to assess whether minimal residual disease (MRD) at the end of induction front-line treatment can serve as a surrogate endpoint for event-free survival (EFS) in childhood B-lineage acute lymphoblastic leukemia. Methods The analysis was based on individual data of 4830 patients from two large phase III trials that asked a randomized question on the effect of different corticosteroids (dexamethasone vs prednisone) during induction chemotherapy on EFS. The association between MRD classified in three ordered categories [negative = 0, low positive = (>0 and <5 × 10−4), and positive = (≥5 × 10-4)] and EFS at the individual and trial levels was evaluated with the meta-analytic approach based on the Plackett copula model. Centers within trial were grouped according to geographical area, and a total of 28 units were identified for the analysis. Results MRD at the end of induction was a poor surrogate for treatment effect on EFS at the trial level, with Rtrial2 = 0.09 (95% confidence interval [CI] = 0.00 to 0.29), whereas at the individual level it was strongly associated with EFS, with an odds ratio of 3.90 (95% CI = 3.35 to 4.44) of failure for patients with higher compared with lower MRD levels. Additional sensitivity and relevant subgroup analyses confirmed these findings at both trial- and patient-level association. Conclusions Although MRD is a robust biomarker highly predictive of outcome for individual patients, clinicians and regulatory bodies should be cautious in using early MRD response in the context of complex multiagent acute lymphoblastic leukemia therapy as an early surrogate endpoint to predict the effect of a randomized treatment intervention on long-term EFS.

scholarly journals Improved results of treatment of adult acute lymphoblastic leukemia

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1242-1248 ◽  
Author(s):  
CA Linker ◽  
LJ Levitt ◽  
M O'Donnell ◽  
CA Ries ◽  
MP Link ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Induction Phase ◽  
Free Survival ◽  
Results Of Treatment ◽  
Kaplan Meier ◽  
Wbc Count ◽  
Disease Free

Abstract We designed a treatment program to improve the outcome for adults with acute lymphoblastic leukemia (ALL). Treatment included a remission- induction phase followed by intensive alternating cycles of non-cross- resistant chemotherapy and prolonged oral maintenance therapy. Eighty- one consecutive previously untreated patients were entered on this study. Ninety-four percent of patients entered complete remission. A Kaplan-Meier analysis predicts that 53% +/- 9% (SEM) of patients in remission will remain free of disease at 3 years. Neither age, sex, WBC count, nor immunophenotype had a significant effect on remission duration. This program of intensive cyclical chemotherapy has improved the disease-free survival of patients with adult ALL.

Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation

Blood ◽  
2009 ◽  
Vol 113 (13) ◽  
pp. 2902-2905 ◽  
Author(s):  
Veronika Bachanova ◽  
Michael R. Verneris ◽  
Todd DeFor ◽  
Claudio G. Brunstein ◽  
Daniel J. Weisdorf
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Transplantation ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Preparative Regimen ◽  
Total Body ◽  
Reduced Intensity

Abstract Twenty-two adult acute lymphoblastic leukemia (ALL) patients (21 of 22 in complete remission [CR]) received reduced-intensity conditioning followed by allogeneic transplantation. All patients were high risk. After a uniform preparative regimen (fludarabine 40 mg/m2 × 5, cyclophosphamide 50 mg/kg, 200 cGy total body irradiation), patients received either matched related (n = 4) or umbilical cord (n = 18) donor grafts. All patients reached neutrophil engraftment and 100% donor chimerism (median, days 10 and 23, respectively). Overall survival, treatment-related mortality (TRM) and relapse were 50% (95% confidence interval [CI], 27%-73%), 27% (95% CI, 9%-45%), and 36% (95% CI, 14%-58%) at 3 years, respectively. There were no relapses beyond 2 years. The cumulative incidence of acute and chronic graft-versus-host disease was 55% and 45%. Hematopoietic cell transplantation in CR1 (n = 14) led to significantly less TRM (8%, P < .04) and improved overall survival (81%, P < .01). For adults with ALL in CR, reduced intensity conditioning allografting results in modest TRM, limited risk of relapse, and promising leukemia-free survival. Clinical trial numbers are NCT00365287, NCT00305682, and NCT00303719.

scholarly journals Reinduction Platform for Children With First Marrow Relapse of Acute Lymphoblastic Leukemia: A Children's Oncology Group Study

2008 ◽  
Vol 26 (24) ◽  
pp. 3971-3978 ◽  
Author(s):  
Elizabeth A. Raetz ◽  
Michael J. Borowitz ◽  
Meenakshi Devidas ◽  
Stephen B. Linda ◽  
Stephen P. Hunger ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Novel Agents ◽  
Late Relapse ◽  
Oncology Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Significant Challenge ◽  
Minimal Residual

Purpose Treatment of childhood relapsed acute lymphoblastic leukemia (ALL) remains a significant challenge. The goal of the Children's Oncology Group (COG) AALL01P2 study was to develop a safe and active chemotherapy reinduction platform, which could be used to evaluate novel agents in future trials. Patients and Methods One hundred twenty-four patients with ALL and first marrow relapse received three, 35-day blocks of reinduction chemotherapy: 69 with early relapse (ER; < 36 months from initial diagnosis) and 55 with late relapse (LR). Minimal residual disease (MRD) was measured by flow cytometry after each treatment block. Results Second complete remission (CR2) rates at the end of block 1 in 117 assessable patients were 68% ± 6% for ER (n = 63) and 96% ± 3% for LR (n = 54; P < .0001). Five of seven patients with T-cell ALL (T-ALL) failed to achieve CR2. Among patients in CR2, MRD greater than 0.01% was detected at the end of block 1 in 75% ± 7% of ER (n = 36) versus 51% ± 8% of LR (n = 43; P = .0375) and 12-month event-free survival was 80% ± 7% versus 58% ± 7% in MRD-negative versus positive patients (P < .0005). Blocks 2 and 3 of therapy resulted in reduction of MRD burden in 40 of 56 patients who were MRD positive after block 1. Toxicity was acceptable during all three blocks with five deaths (4%) from infections. Conclusion The AALL01P2 regimen is a tolerable and active reinduction platform, suitable for testing in combination with novel agents in B-precursor ALL. Alternative strategies are needed for T-ALL. Serial MRD measurements were feasible and prognostic of outcome.

Role of MRD Monitoring in Childhood Acute Lymphoblastic Leukemia after Allogeneic Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 983-983 ◽  
Author(s):  
Adriana Balduzzi ◽  
Sonia Bonanomi ◽  
Monica Manenti Tech ◽  
Maria Dassi ◽  
Giovanni Cazzaniga ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Childhood All ◽  
Log Reduction ◽  
Long Time

Abstract Relapse of acute lymphoblastic leukemia (ALL) after allogeneic transplant has very poor prognosis; whether early prediction of relapse by means of minimal residual disease (MRD) analysis could allow effective treatment is still to be assessed. Eighteen patients at high risk of relapse were prospectively monitored in a single transplant center. MRD analysis and clinical follow up were completed for the first series of 11 patients. This includes 9 males and 2 females (median age 11ys, range 2–16) who received allogeneic hematopoietic cell transplantation (HCT) from compatible (5), one locus mismatched (1) or haploidentical (1) related or unrelated (4) donor for ALL in 1st (5), 2nd (4), or 3rd (2) complete remission (CR), after conditioning regimen containing total body irradiation (TBI) and etoposide (9) or others, and GVHD prophylaxis consisting of cyclosporine, associated with ATG in transplant from other than compatible related donor. Grafts consisted of unmanipulated bone marrow (9), containing a median of 6.6x106CD34+/Kg (range 1.7–8.6) and 57.2x106CD3+/Kg (range 24.4–96.2), or peripheral (1), containing 11x106CD34+/Kg and 174x106CD3+/Kg, or positively selected peripheral (1) containing 12x106CD34+/Kg and 0.04x106CD3+/Kg. Five patients developed grade II–IV acute GVHD, requiring ATG in 4 cases. Five of 11 patients are alive in CR at a median of 15 months (range 11–21), 1 died in CR at 7 months, 5 relapsed at a median of 8 months (range 3–23), and 3 of them died. Patients were monitored by clone-specific RQ-PCR of one (4) or two (7) Ig/TcR markers, with a sensitivity of at least 10−4. At the time of transplant 7 patients were positive at the analysis of the MRD, while 4 were negative; patients were monitored at 1, 3, 6, 9 and 12 months after transplantation, or according to clinical requirements. Among the 4 MRD negative patients, 1 remained negative and is in CR at 19 months, 1 became positive 6 months after unrelated transplant and relapsed 2 months later, 1 relapsed 30 months after haploidentical transplant, a long time after MRD monitoring had stopped, while 1 died in CR. Among the 7 MRD positive patients, 2 remained always MRD positive and relapsed 3 and 7 months after transplant, and 5 experienced MRD negativity at a certain time after transplant; 1 of 5 became MRD positive at the 6th month after transient negativity and relapsed 3 months later, 3 of 5 became negative since the 1st or 3rd month, remained negative, and are alive in CR at 9, 12, and 13 months after transplant, while the remaining 1 alternated negative and positive MRD results and is in CR at 6 months. In 5 patients quantitative MRD data allowed early immunosuppression tapering or discontinuation, yielding severe GVHD in 1, and DLI treatment was planned in 2, but refused in 1; 2 of these 5 are in CR, while 3 relapsed, despite 1 experienced transient MRD 1-log reduction and 1 negativization. In conclusion, MRD monitoring after BMT might direct either early immunosuppression tapering or DLI for prevention of relapse in high risk childhood ALL transplanted patients.

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