Three-Drug Induction and BFM-Type Intensive Consolidation Chemotherapy for Treatment of Standard Risk Childhood Acute Lymphoblastic Leukemia Defined Also by DNA index. The Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) Study ALL-9501.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1951-1951
Author(s):  
Maurizio Arico’ ◽  
Valentino Conter ◽  
Maria Grazia Valsecchi ◽  
Marie France Pinta Boccalatte ◽  
Elena Barisone ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Malignant Neoplasm ◽  
Small Subset ◽  
Unrelated Donor ◽  
Minimal Risk ◽  
Dna Index ◽  
Standard Risk

Abstract In this study, we tried to select a very small subset of children with acute lymphoblastic leukemia (ALL) at minimal risk of treatment failure - identified to not only by early response in vivo, one of the strongest predictors in the I-BFM-SG experience, but also by age, blood count and in particular high DNA content - which we treated with a reduced-intensity BFM schedule. The AIEOP-ALL 9501 study enrolled patients with standard-risk (SR) ALL, defined as: <20,000 WBC/mm3, age 1 to <6 years, non-T immunophenotype, DNA index between 1.16 and 1.6, non t(9;22), no extramedullary leukemia, good response to prednisone (PGR, defined as <1,000/mmc blasts in the peripheral blood after 7 days of prednisone and one injection of IT-MTX), CR at the end of induction therapy. Follow-up was updated at December,31st 2003 and median follow-up was 5.9 years. Treatment consisted of a modified BFM schedule: 3-drug (VCR + PDN + Erwinia ASP), 43-day induction, no phase IB, 4x2 g/m2 MTX, reinduction with protocol II followed by 6MP+MTX continuation therapy up to 2 years; CNS directed therapy consisted of IT-MTXx18. Between May 95 and August 2000, 137 patients were identified as SR (7.8% of the ALL-95 population), of whom 102 received the SR protocol and are here reported.Of them, 1 died in remission of septicemia, and 1 had developed a second malignant neoplasm (T-ALL after initial B-lineage ALL); 11 patients relapsed (bone marrow, n=8; central nervous system, n=1; marrow + testis, n=1; eye, n=1) and their re-treatment included chemotherapy only (n=3, 1 dead) or plus bone marrow transplant (n=8) either autologous (n=2) or allogeneic from matched (n=4, 1 dead) or partially matched (n=2) unrelated donor. The remaining 89 are in first CR; the probabilities (and related standard errors) of survival and event-free survival (EFS) were 97.0% (1.7) and 86.7% (3.5) at 5 years, 95.3% (2.4) and 86.7% (3.5) at 7 years, respectively. There was no difference in the outcome between the 56 females [7 events, 7-yrs EFS, 87.3 (4.5)] and the 46 males [6 events, 85.9 (5.4)]. Although most of the relapsed patients were rescued, the long-term EFS in this small, very selected group of patients remains inferior to expectance. Thus, alternative selection criteria, for instance related to minimal residual disease as in current AIEOP-ALL 2000, should be considered in order to address the issue of treatment reduction.

scholarly journals Translocation (9;22) is associated with extremely poor prognosis in intensively treated children with acute lymphoblastic leukemia

Blood ◽  
1991 ◽  
Vol 77 (3) ◽  
pp. 435-439 ◽  
Author(s):  
JA Fletcher ◽  
EA Lynch ◽  
VM Kimball ◽  
M Donnelly ◽  
R Tantravahi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Poor Prognosis ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Intensive Treatment ◽  
First Remission ◽  
Prognostic Implications

Abstract The prognostic implications of t(9;22)(q34;q11) were assessed at a median follow-up of 3.5 years in 434 children receiving intensive treatment for acute lymphoblastic leukemia (ALL). Four-year event-free and overall survivals were 81% and 88%, respectively, in 419 children lacking t(9;22), but were 0% and 20%, respectively, in 15 children with t(9;22) (P less than .001). Poor outcome for children with t(9;22)- positive ALL was particularly notable because we have reported improved survival in other historically poor prognosis ALL cytogenetic categories when treated with similarly intensive therapy. We recommend that very intensive treatment approaches, including bone marrow transplantation in first remission, be considered for all children with t(9;22)-positive ALL.

scholarly journals CD2 antigen expression on leukemic cells as a predictor of event-free survival after chemotherapy for T-lineage acute lymphoblastic leukemia: a Children's Cancer Group study

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4288-4295 ◽  
Author(s):  
FM Uckun ◽  
PG Steinherz ◽  
H Sather ◽  
M Trigg ◽  
D Arthur ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Antigen Expression ◽  
Leukemic Cells ◽  
Event Free Survival ◽  
Free Survival ◽  
Cancer Group ◽  
Standard Risk

Abstract We examined the prognostic impact of CD2 antigen expression for 651 patients with T-lineage acute lymphoblastic leukemia (ALL), who were enrolled in front-line Childrens Cancer Group treatment studies between 1983 and 1994. There was a statistically significant correlation between the CD2 antigen positive leukemic cell content of bone marrow and probability of remaining in bone marrow remission, as well as overall event-free survival (EFS) (P = .0003 and P = .002, log-rank tests for linear trend). When compared with patients with the highest CD2 expression level (> 75% positivity), the life table relative event rate (RER) was 1.22 for patients with intermediate range CD2 expression level (30% to 75% positivity) and 1.81 for “CD2-negative” patients (< 30% positivity). At 6 years postdiagnosis, the EFS estimates for the three CD2 expression groups (low positivity to high positivity) were 52.8%, 65.5%, and 71.9%, respectively. CD2 expression remained a significant predictor of EFS after adjustment for the effects of other covariates by multivariate regression, with a RER of 1.47 for CD2- negative patients (P = .04). Analysis of T-lineage ALL patients shows a significant separation in EFS after adjustment for the National Cancer Institute (NCI) age and white blood cell (WBC) criteria for standard and high-risk ALL (P = .002, RER = 1.67). The determination of CD2 expression on leukemic cells helped identify patients with the better and poorer prognoses in both of these risk group subsets. For standard risk T-lineage ALL, CD2-negative patients had a worse outcome (P = .0007, RER = 2.92) with an estimated 5-year EFS of 55.9% as compared with 78.3% for the CD2-positive patients. Thus, CD2 negativity in standard risk T-lineage ALL identified a group of patients who had a worse outcome than high-risk T-lineage ALL patients who were CD2 positive. The percentage of CD2 antigen positive leukemic cells from T- lineage ALL patients is a powerful predictor of EFS after chemotherapy. This prognostic relationship is the first instance in which a biological marker in T-lineage ALL has been unequivocally linked to treatment outcome.

Early Evaluation of Bone Marrow Minimal Residual Disease by Flowcytometry on Day 15 Is Feasible on a Multicenter Basis and Bears Strong Prognostic Value in Childhood Acute Lymphoblastic Leukemia. The AIEOP-BFM Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1423-1423
Author(s):  
Giuseppe Basso ◽  
Giuseppe Gaipa ◽  
Maria Grazia Valsecchi ◽  
Marinella Veltroni ◽  
Michael Dworzak ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Reference Laboratory ◽  
Intermediate Risk ◽  
Early Measurement ◽  
Relapse Risk ◽  
Standard Risk ◽  
Risk Of Relapse

Abstract Early measurement of blast clearance is a relevant prognostic indicator in childhood acute lymphoblastic leukemia (ALL). To this purpose we measured, by four-colour flowcytometry (FC), the percentage of blast cells in bone marrow samples from Italian patients enrolled in the multicentre AIEOP-BFM ALL 2000 trial. Samples were collected on day 15 (after 14 days of steroids, and one dose of IT-MTX, vincristine, daunorubicine, asparaginase) and shipped overnight to the reference laboratory. The data were compared to PCR-MRD performed, by study design, on day +33 and +78 BM samples. We report the results of patients enrolled between December 2000 and October 2004. The 561 patients studied were not different from the remaining ones (with no available material) including their cumulative incidence of relapse (SE): 17.3% (1.9) vs. 18.1% (1.5) in 850 patients not studied. According to the results of FC-MRD, 5 groups were defined: negative (blast count &lt;0.01%, n=143), &lt;0.1% (n=94), &lt;1% (n=149), 1–10% (n=119), &gt;10% (n=56). Their cumulative 5-year risk of relapse was: 4.1% (1.9), 9.3% (4.0), 14.3% (3.2), 26.5% (5.5), 53.7% (7.4), respectively. By PCR-MRD, the same patients were stratified as follows: 177 were standard risk and had 5-year risk of relapse of 4.1% (1.7), 233 at intermediate risk had a relapse risk of 24.2% (3.4), 37 at high risk had a relapse risk of 58.1% (9); the remaining 124 patients (21.6%) were not stratified by PCR-MRD due to lack of 2 sensitive (≥10−4) markers. Of 177 patients classified as standard risk by PCR (double negative), 110 fell within the 2 subgroups with lower FC-MRD (&lt;0.1%), 46 had &lt;1%, 19 had &lt;10%, only 2 &gt;10% of blasts. Of the 233 patients stratified as PCR-MRD intermediate risk (d78 &lt;10−3), FC-MRD related groups had the following probabilities of EFS: 93.5% (3.6; n=47), 83.3%(8.0; n=30), 80.5%(5.1; n=70), 66.5%(10.8; n=57), 39.2%(11.8; n=29). We conclude that very early measurement of FC-MRD on day 15 bone marrow is feasible in our multicentre cooperative setting. On the basis of our data we suggest the following risk groups: standard, when &lt;0.1% blasts on day 15 BM; intermediate for 0.1 to &lt;10%; high, for &gt;10% blasts. These groups had a risk of relapse of 6.2% (1.9), 19.5% (3), and 53.7% (7.4), respectively. Since it is fast, reproducible, relatively cheap and applicable to virtually all patients, our group decided to apply it prospectively on all ALL patients to integrate PCR-based stratification. Our findings showed that: early (d15) MRD detection by FCM identifies different patients than PCR on d33 and d78; FCM may be very useful to identify earlier the highly sensitive ALL with low relapse risk (even though long-term follow-up is still missing), whereas later timepoints may be accessible for PCR and the identification of HR patients.

Prognostic Impact of Bone Marrow B Lymphocyte Precursors (hematogones) Detection in 95 Acute Lymphoblastic Leukemia Cases

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4791-4791 ◽  
Author(s):  
Sylvain P Chantepie ◽  
Audrey Emmanuelle Dugué ◽  
Patrice Chevallier ◽  
Aline Schmidt-Tanguy ◽  
Véronique Salaün ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Prognostic Impact ◽  
Hematopoietic Stem ◽  
Time Points ◽  
Number Of Patients

Abstract Abstract 4791 Acute lymphoblastic leukemia (ALL) multiparameter flow cytometry (MFC) study of bone marrow aspiration after chemotherapy is crucial for determining minimal residual disease (MRD). Hematogones (HGs) have to be distinguishing from leukemic cells in B-cell subtypes and could be quantify during follow-up. To date, the incidence of Hgs in ALL and their prognostic significance have not been investigated. The aim of this multicenter study was to quantify Hgs after chemotherapy in ALL adult patients and to define its prognostic value. We retrospectively analyzed the incidence of HGs in 95 ALL patients, 71 with B-ALL (75%), 24 (25%) with T-ALL in first line treatment. The median age was 37 years [8–71], 20% had t(9;22) cytogenetic abnormality, and 70% had abnormal karyotype. 4/5-color MFC analysis MRD and HGs were performed at different time point (TP) after diagnosis: TP1 (post-induction, day 45 [41–61], n=78), TP2 (post-consolidation, day 111 [94–144] 25, n=42), TP3 (post-intensification/before hematopoietic stem cell transplantation (HSCT), day 179 [125–268], n=58), TP4 (n=11), TP5 (n=17), TP6 (n=9) after a median of 33, 91 and 167 days after HSCT, respectively. A total of 39 patients (41%) relapsed with a median of 26 months [7.7–47.9]. Forty seven patients (50%) received an HSCT in a complete (98%) or partial remission (2%). At TP1, TP2, TP3, TP4, TP5, TP6, the median HGs [range] were as followed: 0.00 [0.00–6.90]%, 0.30 [0.00–11.2]%, 0.98 [0.00–33.00]%, 0.52 [0.00;23.00]%, 5.50 [0.00;25.00]%, 4.60 [0.00;34.00]%, 5.90 [0.32;11.80]%, respectively. Figure 1 showed the percentage of patients with negative MRD (Figure 1A) and detectable HGs (figure 1B) during the follow up of ALL patients. There is a progressive increase of the percentage of patients with detectable HGs during the time of treatment and follow-up. Interestingly, there was no correlation between age and HGs level while in physiological situation the HGs rate decreases with increasing age. There was a negative correlation between positive MRD and detectable HGs at TP1 (p=0.022) but not at TP3 (p=0.88). In univariate analysis positive MRD at P1 and P3, age (/10), the presence of t(9;22) and absence of HGs at TP3 (figure 2) were bad prognostic factors for relapse free-survival (RFS) and overall survival (OS). The presence of HGs at other different time of evaluation was not associated with a significant decrease of relapse or death. However, patients who had a negative MRD at TP1 and detectable HGs in the bone marrow at TP3 exhibited a better RFS and OS (p=0.018 and p=0.065 respectively). Patients who had negative MRD at TP3 and had detectable HGs at TP3 had also a better RFS and OS (p=0.007 and p=0.011, respectively) compared to patients with negative MRD at TP3 and without HGs (figure 3). In patients who had a positive MRD at TP1, detectable HGs at TP3 identified a subgroup of patient with favorable OS compared to patient with positive MRD at TP1 and without detectable HGs (p=0.072). These results should be taken with cautious because of the decreasing number of patients evaluated at different time points. However, HGs analysis could represent a new area of investigation in search of new prognostic factors in the context of adult ALL. Figure 1. Percentage of patients with (A) negative MRD and (B) detectable HGs at different time points after starting of treatment. Figure 1. Percentage of patients with (A) negative MRD and (B) detectable HGs at different time points after starting of treatment. Figure 2. Overall survival according to HGs status at TP3. Figure 2. Overall survival according to HGs status at TP3. Figure 3. Overall survival in patients with negative MRD at TP3 according to HGs status. Figure 3. Overall survival in patients with negative MRD at TP3 according to HGs status. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Unrelated donor transplants in adults with Philadelphia-negative acute lymphoblastic leukemia in first complete remission

Blood ◽  
2008 ◽  
Vol 112 (2) ◽  
pp. 426-434 ◽  
Author(s):  
David I. Marks ◽  
Waleska S. Pérez ◽  
Wensheng He ◽  
Mei-Jie Zhang ◽  
Michael R. Bishop ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
T Cell Depletion ◽  
First Complete Remission ◽  
Related Mortality

Abstract We report the retrospective outcomes of unrelated donor (URD) transplants in 169 patients with acute lymphoblastic leukemia (ALL) in first complete remission (CR1) who received transplants between 1995 and 2004. Median age was 33 years (range, 16-59 years). A total of 50% had a white blood cell count (WBC) more than 30 × 109/L, 18% extramedullary disease, 42% achieved CR more than 8 weeks from diagnosis, 25% had adverse cytogenetics, and 19% had T-cell leukemia. A total of 41% were HLA well-matched, 41% partially matched with their donors, and 18% were HLA-mismatched. At 54-month median follow-up, incidences of acute grade 2-IV, III to IV, and chronic graft-versus-host disease were 50%, 25%, and 43%, respectively. Five-year treatment-related mortality (TRM), relapse, and overall survival were 42%, 20%, and 39%, respectively. In multivariate analyses, TRM was significantly higher with HLA-mismatched donors and T-cell depletion. Relapse risk was higher if the diagnostic WBC was more than 100 × 109/L. Factors associated with poorer survival included WBC more than 100 × 109/L, more than 8 weeks to CR1, cytomegalovirus seropositivity, HLA mismatching, and T-cell depletion. Nearly 40% of adults with ALL in CR1 survive 5 years after URD transplantation. Relapse risks were modest; TRM is the major cause of treatment failure. Selecting closely HLA-matched URD and reducing TRM should improve results.

scholarly journals Translocation (9;22) is associated with extremely poor prognosis in intensively treated children with acute lymphoblastic leukemia

Blood ◽  
1991 ◽  
Vol 77 (3) ◽  
pp. 435-439
Author(s):  
JA Fletcher ◽  
EA Lynch ◽  
VM Kimball ◽  
M Donnelly ◽  
R Tantravahi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Poor Prognosis ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Intensive Treatment ◽  
First Remission ◽  
Prognostic Implications

The prognostic implications of t(9;22)(q34;q11) were assessed at a median follow-up of 3.5 years in 434 children receiving intensive treatment for acute lymphoblastic leukemia (ALL). Four-year event-free and overall survivals were 81% and 88%, respectively, in 419 children lacking t(9;22), but were 0% and 20%, respectively, in 15 children with t(9;22) (P less than .001). Poor outcome for children with t(9;22)- positive ALL was particularly notable because we have reported improved survival in other historically poor prognosis ALL cytogenetic categories when treated with similarly intensive therapy. We recommend that very intensive treatment approaches, including bone marrow transplantation in first remission, be considered for all children with t(9;22)-positive ALL.

Evaluation of the differences between extramedullary and bone marrow relapse in adult acute lymphoblastic leukemia patients in terms of clinical features and survival outcomes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19516-e19516
Author(s):  
Nilgun Sayınalp ◽  
Rafiye Ciftciler ◽  
Yahya Buyukasik ◽  
IC Haznedaroglu ◽  
Salih Aksu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Clinical Features ◽  
Lymphoblastic Leukemia ◽  
Care Center ◽  
Tertiary Care ◽  
Survival Outcomes ◽  
Hematopoietic Stem ◽  
Significant Difference

e19516 Background: Acute lymphoblastic leukemia (ALL) in adult patients is an uncommon and difficult-to-treat hematological malignancy that is characterized by excess lymphoblasts in the bone marrow (BM). Although many patients achieve remission with chemotherapy, relapse rates are high and survival outcomes in adults are worse than pediatric patients. With uncontrolled proliferation and accumulation of these lymphoblasts, normal hematopoiesis is suppressed and infiltrates various extramedullary (EM) regions. The aim of this study is to evaluate the difference between EM and BM relapse in adult ALL patients in terms of clinical features and survival outcomes. Methods: In this study, we retrospectively analyzed 108 patients who were diagnosed as ALL and treated in our tertiary care center between 2003 and 2019. Statistical analyses were performed using the SPSS software version 25. Results: The study included 108 patients, consisting of 64 males and 44 females with a median age of 30 (range: 17-79 years). The majority of cases were B-cell in origin; 87 (80.6%) patients had B-ALL and 21 (19.4%) had T-ALL. Median follow-up duration for all patients was 21.1 months (range: 0.49-158.7 months). In the follow-up, 28 patients (25.9%) were received allogeneic hematopoietic stem cell transplantation. A total of 27 (25%) patients relapsed during the follow-up period. In 15 (13.9%) of 27 patients, only BM relapse was observed. EM relapse was observed in 12 (11.1%) patients. EM localizations were identified: brain [n = 2, 1.8%], lung [n = 1, 0.92%], retroperitoneum region [n = 1, 0.92%], kidney [n = 2, 1.8%], breast [n = 1, 0.92%], vertebral column [n = 3, 2.7%], spleen [n = 1, 0.92%], and uvea [n = 1, 0.92%]. All of the patients relapsed with bone marrow were B-ALL. Five of the patients (41.7%) with EM relapse were T-ALL (p = 0.006). No significant difference was observed in terms of gender (p = 0.16) and age (p = 0.12) in patients with BM relapse and EM relapse. Median overall survival (OS) was 42.3 months (95% CI: 15.6-69.0) for patients with BM relapse and 32.8 months (95% CI: 20.0-45.5) for patients with EM relapse (p = 0.42). Conclusions: In conclusion, EM relapse is common in ALL patients. We observed that EM relapse is more frequent, especially in patients with T-ALL cell origin. no significant difference was observed in both groups in terms of OS. ALL patients should be carefully followed up in terms of EM relapses as well as bone marrow relapse.

Inotuzumab Ozogamicin (IO) Is An Effective Salvage Therapy That Allows for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Remission in Patients with Advanced Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3102-3102
Author(s):  
Partow Kebriaei ◽  
Kaci Wilhelm ◽  
Farhad Ravandi ◽  
Rima M. Saliba ◽  
Marcos De Lima ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Salvage Therapy ◽  
Lymphoblastic Leukemia ◽  
Unrelated Donor ◽  
Inotuzumab Ozogamicin ◽  
Hematopoietic Stem ◽  
Conditioning Regimens

Abstract Abstract 3102 No highly effective salvage therapy exists for patients with relapsed acute lymphoblastic leukemia (ALL). Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody attached to calicheamycin and targets B lymphocytes in early stages of development. A 56% overall response rate was noted in a Phase I study of single agent IO in patients with refractory ALL (Jabbour ASCO 2011), enabling subsequent transplant in remission in a relatively large number of patients. Of note, in the year prior to the availability of IO, we consulted on 13 patients will ALL beyond second remission and transplanted 5 (38%), and after the availability of IO, we consulted on 41 patients and transplanted 27 (67%). Methods: We describe our findings in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) following treatment with IO between June 2010 and May 2011. IO was administered at 1.8 mg/m2 IV every 3 weeks. Results: 19 patients with median age 32 years (range 5–60) received an allogeneic matched sibling (n=6), matched unrelated donor (n=8), mismatched unrelated donor (n=4), or cord blood HSCT (n=1) in complete remission (CR) (n=2), CR without platelet recovery (n=14), and active disease (n=3); 10 patients were MRD negative at time of HSCT as determined by multiparameter flow cytometry. Patients had received 2 (n=3), 3 (n=9), 4 (n=4), 5 (n=2), or 6 (n=1) lines of salvage therapy prior to HSCT, including 3 patients who had received a prior allogeneic HSCT; IO was the last agent in 17 patients (2 patients refractory to IO received other therapy prior to HSCT). Patients received 1 (n=1), 2 (n=9), 3 (n=6), 4 (n=2), or 5 (n=1) courses of IO a median of 35 days (range 18–69) prior to transplant conditioning with busulfan (Bu) and colafarabine (Clo) (n=8), BuClo+ thiotepa (TT) (n=4), fludarabine (Flu) and melphalan (Mel) (n=1), FluMelTT (n=3), or etoposide and total body irradiation (TBI) (n=3); GVHD prophylaxis was tacrolimus-based for all patients, with post-HSCT cyclophosphamide added for patients receiving mismatched unrelated donors. With a median follow-up of 3 months among surviving patients (0.6–8.2), overall and progression-free survival is 59% at 3 months. There were 11 deaths, 6 from relapse, 4 from multi-organ failure involving VOD, and 1 from pneumonia. Transient liver enzyme elevations were noted in all of the patients, with 26% (n=5) patients developing VOD. The development of VOD was associated with greater lines of prior therapy prior to HSCT (3–5 lines prior salvage therapy, including 2 patients who had a prior allo-HSCT) and more intense transplant conditioning regimens (4 of the 5 patients received BuCloTT or FluMelTT). Conclusions: IO is an effective salvage therapy in patients with advanced ALL, allowing more patients to receive HSCT with encouraging response rates. Longer follow-up is needed to more completely assess disease control. Using reduced intensity HSCT conditioning regimens and avoiding multiple lines of prior therapies may result in less hepatic toxicity. Disclosures: O'Brien: Pfizer: Consultancy. Kantarjian:Pfizer: Research Funding.

Encouraging Outcomes of Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Patients with Acute Lymphoblastic Leukemia in Second Complete Remission

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5933-5933
Author(s):  
Kohei Higuchi ◽  
Maho Sato ◽  
Osamu Kondo ◽  
Aya Ioi ◽  
Azusa Mayumi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Abstract [Background] We have been performing reduced-intensity stem cell transplantation (RIST) to avoid preconditioning-related complications. However, the effectiveness of RIST in pediatric patients with acute lymphoblastic leukemia (ALL) remains to be clarified. [Methods] We retrospectively reviewed 37 pediatric patients with ALL in second complete remission (CR2) who underwent first allogeneic hematopoietic stem cell transplantation (allo-SCT) between 1993 and 2012 in our institute. We compared the outcomes of RIST with those of myeloablative stem cell transplantation (MAST). [Results] The median age at allo-SCT was 9 years (range, 1 to 18 years). There were 33 B-lineage ALL, 3 T-lineage ALL, 1 lineage unknown ALL, and none of Philadelphia chromosome-positive ALL. Sixteen patients received HLA-matched bone marrow (7 related; 9 unrelated), 12 HLA-mismatched bone marrow (11 unrelated; 1 HLA haploidentical related), 4 cord blood, and 5 CD34 positive peripheral blood stem cells (HLA haploidentical related). In all patients, the 5-year overall survival (5y-OS) rate and the 5-year event free survival (5y-EFS) rate were 75.1% and 56.5%, respectively. Seven patients underwent RIST and 30 patients underwent MAST. The median follow-up durations of RIST and MAST groups were 3.3 years (range, 0.9 to 8.2 years) and 11.3 years (range, 0 to 21.2 years), respectively. The 5y-OS rates in RIST and MAST groups were 85.7% and 59.8%, and the 5y-EFS rates were 71.4% and 53.3%, respectively. The 5-year cumulative transplant-related mortality (TRM) rates in RIST and MAST groups were 0% and 31.0%, and the 5-year cumulative relapse rates were 28.6% and 24.3%, respectively. [Discussion] In our series, the cumulative relapse rate in RIST group was similar with that in MAST group, and the cumulative TRM rate in RIST group was lower than that of MAST group. Therefore, both of the 5y-OS and the 5y-EFS rates in RIST group seem to be better than those in MAST group. The outcomes of RIST in our series do not seem to be poorer. Although further studies are needed because of the small size of patients and short follow-up duration, RIST can be considered as the first transplantation for pediatric patients with ALL in CR2. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

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