scholarly journals 240: Reduced-intensity stem cell transplantation in patients with high-risk acute lymphoblastic leukemia (ALL)

2007 ◽  
Vol 13 (2) ◽  
pp. 88
Author(s):  
C.H. Gutierrez-Aguirre ◽  
G.J. Ruiz-Argüelles ◽  
O.G. Cantu-Rodriguez ◽  
O. Gonzalez-LLano ◽  
D. Gomez-Almaguer
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Reduced Intensity

scholarly journals Intensive Chemotherapy Along with Aggressive Supportive Care Can Spare Stem Cell Transplantation in a Subset of Patients without Compromising an Outcome in Infants with Acute Lymphoblastic Leukemia; A Report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Trial MLL-10

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2626-2626
Author(s):  
Daisuke Tomizawa ◽  
Takako Miyamura ◽  
Toshihiko Imamura ◽  
Tomoyuki Watanabe ◽  
Akiko Moriya Saito ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Supportive Care ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Intensive Chemotherapy ◽  
Free Survival ◽  
Cns Disease

BACKGROUND: Outcome of infants with acute lymphoblastic leukemia (ALL), especially those with rearrangement of MLL (KMT2A) gene (MLL-r), is extremely poor. A strategy to perform allogeneic hematopoietic stem cell transplantation (HSCT) for all the infants with MLL-r ALL in first remission (1CR) have been tested in the previous Japanese trials MLL96/98/03, however, the improvement was modest. Given the recent evidence of a limited role of HSCT especially in infants lacking poor prognostic factors, efficacy and safety of an intensive chemotherapy and risk stratification to limit HSCT for only infants with high-risk of relapse were evaluated in the JPLSG MLL-10 trial (UMIN000004801). PATIENTS & METHODS: Infants age less than 365 days with ALL were registered in the MLL-10 study and were stratified by their MLL gene status, age at diagnosis, and presence of CNS disease; low-risk (LR), if the patients had germline MLL gene (MLL-g); intermediate-risk (IR), if the patients with MLL-r ALL were age 180 days or older and lack CNS disease; high-risk (HR), if the patients with MLL-r ALL were age <180 days or having CNS disease. All the infants with MLL-r ALL received Interfant induction followed by COG AALL0631 post-remission chemotherapy with modification of adding high-dose cytarabine in early intensification phase. All the HR cases were allocated to HSCT in 1CR. LR cases were treated based on the Japanese MLL96/98 MLL-g chemotherapy. Minimal residual disease (MRD) was evaluated in 3 methods, flowcytometry, PCR of MLL fusion transcripts, and PCR targeting IgH/TCR rearrangements, but were not used to guide therapies. RESULTS: A total of 90 eligible infants with ALL were registered in the MLL-10 study between Jan/2011 and Dec/2014; 15 cases were stratified as LR, 19 as IR, and 56 as HR. Remission status was evaluated after 2 chemotherapy courses; 82 (91.1%) achieved 1CR, 3 failed to achieve 1CR, and 5 discontinued the trial before CR evaluation. No early death was observed. With median follow-up period of 1954 days (range, 534-2835 days) in the live patients, 3-year probability of event-free survival (pEFS) and overall survival (pOS) were 70.9% (95% CI, 60.0-79.3%) and 86.6% (77.6-92.2%), respectively. Among the MLL-r cases, 3-year pEFS and pOS were 66.2% (53.9-75.9%) and 83.9% (73.4-90.5%), respectively. According to the risk groups, 3-year pEFS were 93.3% (61.2-99.0%) for LR, 94.4% (66.6-99.2%) for IR, and 56.6% (42.4-68.6%) for HR cases. Regarding the MRD studies, correlation of MRD results in 3 methodologies seemed reasonable, but while flow-MRD could be evaluated in 85 cases, MLL-fusion PCR-MRD (MLL-r cases only) and IgH/TCR PCR-MRD could only be evaluated in 55 and 50 cases, respectively. In the univariable analysis for MLL-r cases, female sex (P=0.04), younger age at diagnosis (P=0.01), and 0.01%< flow-MRD after 2 courses of chemotherapy (P<0.01) had negative impact on pEFS. In multivariable analysis, female sex (P=0.01) and positive flow-MRD (P<0.01) were poor prognostic. Among the 38 HR cases who received HSCT in 1CR per protocol, 3-year probability of disease-free survival was 65.7% (48.3-78.4%) and only one non-relapse death was observed. CONCLUSIONS: Introduction of intensive chemotherapy enabled us to spare allogeneic HSCT in 1CR at least in a subset of infants with MLL-r ALL without compromising their outcome. This was accomplished also because of the aggressive supportive care provided to the study cases, such as full hospitalization during and after the intensive treatment phases, intensive use of rasburicase to prevent tumor lysis syndromes, and aggressive infection prophylaxis. However, outcome of HR MLL-r cases is still unsatisfactory, and introduction of novel agents is mandatory for further improvement in the outcome of infants with ALL. Figure Disclosures No relevant conflicts of interest to declare.

No Impact of Adverse Karyotype on Outcome after Allogeneic Stem Cell Transplantation in Patients with High-Risk Acute Lymphoblastic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3152-3152
Author(s):  
Ingo Tamm ◽  
Gero Massenkeil ◽  
Mandy Wagner ◽  
Theis Terwey ◽  
Christoph Lutz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Normal Karyotype ◽  
Chromosomal Anomalies

Abstract Karyotypes like Philadelphia-chromosome (Ph+) and t(4;11) adversely influence clinical outcome in adult patients with acute lymphoblastic leukemia (ALL) after chemotherapy. Here, we analyze the potential impact of karyotype on outcome after allogeneic hematopoietic stem cell therapy (HSCT) in ALL. We present a retrospective analysis of 135 adult ALL patients treated unicentrically within the German ALL (GMALL) protocol using allogeneic HSCT. All patients were high-risk patients in CR1 according to GMALL definitions (i.e., WBC > 30.000/μl, pro-B-ALL, t(4;11), t(9;22), early T- or mature T-ALL, no CR after first induction) or were beyond CR1. Median age of all patients was 29 years (range 16 – 55), 99 B-lineage and 36 T-lineage ALLs were transplanted. Normal karyotype was present in 57 patients, Ph+ in 36 patients, complex chromosomal anomalies in six patients, t(4;11) in five patients, other aberrations in 22 patients and no growth/no cytogenetic data were available for 9 patients. Patients were transplanted in complete remission (CR) CR1 (60), CR2 (23), CR3 (7), first relapse (30), second relapse (6), third relapse (1) and eight patients had primary induction failure. 41 patients received bone marrow and 94 patients received peripheral blood stem cell transplants. Patients received standard high-dose (n=125) or reduced intensity conditioning (RIC) (n=10) HSCT from related (n=58) or unrelated (n=77) donors. Overall, after a median follow-up of 11 months (range 1–120), 74 (55%) patients died and 61 (45%) are alive. Median follow-up of the living is 29 months (range 1–120). Deaths were due to treatment-related mortality (TRM; n=33; 24%) or relapse (n=41; 31%). Leukemia-free survival (LFS), overall survival, and TRM were not significantly different between the karyotype subgroups studied. LFS at 6 months, 1 year, 3 years, and five years was 62%, 60%, 50%, and 41% for patients with a normal karyotype; 63%, 47%, 40%, and 28% for patients with Ph+; and 61%, 40%, 27%, and 27% for patients with other aberrations. 4/5 patients with t(4;11) and 4/6 patients with complex chromosomal abnormalities are alive in CR. In conclusion, there is no adverse impact of classical poor risk karyotypes on outcome within this high-risk group of ALL patients after allogeneic stem cell transplantation. In contrast, there was a trend that patients with t(4;11) and complex chromosomal anomalies did better (4/5 alive, 1/5 TRM and 4/6 alive, 1/6 TRM, 1/6 relapse, respectively) than patients with other aberrations (8/22 alive, 8/22 death due to relapse, 6/22 TRM). High-risk ALL patients with poor risk cytogenetics are candidates for allogeneic stem cell transplantation which can be curative. Whether other conditioning regimens or adoptive immunotherapy can reduce relapse rate in this patient group is a matter of ongoing clinical research.

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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