Does ATRA Confirm to Play a Role in the Better Relapse Free Survival of Infants with Acute Lymphoblastic Leukemia?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1515-1515
Author(s):  
Larisa Fechina ◽  
Egor Shorikov ◽  
Olga Streneva ◽  
Olga Khlebnikova ◽  
Igor Vyatkin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Molecular Mechanisms ◽  
Treatment Approach ◽  
Lymphoblastic Leukemia ◽  
Relapse Free Survival ◽  
Standard Chemotherapy ◽  
Free Survival ◽  
Cox Regression Analysis

Abstract Abstract 1515 Treatment achievements in infant's acute lymphoblastic leukemia (ALL) are still very modest. Despite of many attempts, the creation of novel, based on the molecular mechanisms, clinically approved and safe therapy strategies for this group of patients (pts) seems to be slow, so far. We also have developed a new treatment approach for infants with acute leukemia – MLL-Baby protocol, which includes 1 or 2 weeks ATRA consecutive courses at the dosing schedule of 25 mg/m2/d adjusted to age, started immediately after induction completion, alternating with standard chemotherapy and/or simultaneously applied with re-inductions. Rationale for ATRA application and MLL-Baby details were introduced in our previous report (ASH 2007 Abstract #2828). We have described there a small group of 19 primary diagnosed ALL infants, who underwent MLL-Baby protocol treatment in comparison to the group treated by standard chemotherapy with 20 months (mo.) median of follow up. ATRA-containing regimen has been shown well tolerated and improved early relapse free survival (RFS) significantly. Aim. To re-assess the ATRA efficacy in more representative group of pts with longer time of follow up. From September 2003 108 pts with primary ALL younger 12 mo. were non-randomly allocated either to ATRA (+) treatment approach (MLL-Baby) – 75 pts or ATRA (-) standard chemotherapy (mainly ALL-MB) – 33 pts due to decision of the treating physicians from 24 participating clinics in Russia and Belarus. Parents' informed consent was signed in all cases. The trial was approved by Ethics Committees. Both ATRA (−) and ATRA (+) groups were similar by the initial characteristics: median age 6 (1–11) and 6 (0–11) mo.; m/f ratio 12/21 and 25/50; initial WBC 96,7 (0,7–940) and 83,9 (1,6–2058) per microliter respectively, although CNS involvement seems to be more frequent in ATRA (+) group: 4 (12%) and 18 (24%) pts correspondingly. MLL rearrangements (MLL pos.) were found in 15 (53,6%) from 28 examined ATRA (−) pts and in 53 (70,7%) from 75 ATRA (+) pts. BI phenotype predominance was evident in ATRA (+) group - 39 (52,7%) out of 74 examined pts. The number of pts who have achieved CR was equally high in both schedules: 28 (84,9%) and 67 (89,3%) but the relapses rates remains significantly different: 16 (57,1%) and 16 (23,8%) pts in ATRA (-) and ATRA (+) groups respectively (p=0,001). Eight years RFS is 0,36 ± 0,08 and 0,59 ± 0,06 (p=0,02); cumulative incidence of relapses (RCI) is 0,62 ± 0,01 and 0,31 ± 0,004 (p=0,03) in ATRA (−) and ATRA (+) groups correspondingly, although EFS: 0,54 ± 0,06 vs. 0,33 ± 0,08 (p=0,17) and OS: 0,59 ± 0,06 vs. 0,36 ± 0,08 (p=0,09), median of follow up - 36 mo. (2 - 105), did not differ significantly between 2 groups ATRA (+) and ATRA (−) respectively due to the high proportion of induction and remission deaths. Among 75 pts treated by MLL-Baby – 7 (9,3%) died in induction and 7 (10,4%) out of 67 pts who achieved CR died in remission with median time to death – 2 mo., mostly because of severe infections. Out of 46 MLL pos. pts from ATRA (+) group who achieved CR, 14 (30%) pts relapsed, RFS is 0,59 ± 0,08 and RCI 0,40 ± 0,007. In contrast, in ATRA (−) group the relapse incidence in MLL pos. pts was very high - 12 (80%) out of 15 pts who achieved CR (p=0,008), RFS is 0,20 ± 0,10 (p=0,01) and RCI 0,80 ± 0,01 (p=0,02) correspondingly. In univariate analysis the following risk-factors: age < 6 mo. (p=0,001); MLL rearrangements (p=0,004) and dexamethasone response on Day 8 (p=0,01) have a significant negative impact on EFS in group of pts treated by MLL-Baby. Cox-regression analysis confirms the negative value of the same risk-factors: MLL pos. status with Hazard Ratio (HR) 3,8 (95% CI 1,32-10,9) p=0,01; age HR 3,18 (95%CI 1,5–6,8) p=0,003 and Day 8 response HR 3,16 (95% CI 1,4–7,1) p=0,005. Conclusions. The updated results in our cohort of 75 patients demonstrated that ATRA confirms effectiveness in the relapses prevention in infants suffering from ALL, if used in combination with standard chemotherapy without any escalation and bone marrow transplantation. Although the molecular mechanisms of ATRA effect are still poorly understood and need to be deeply explored, it might be recommended for randomization within representative international studies, particularly to the MLL rearranged infant's ALL. Great efforts in non-relapse mortality reduction should be applied by all participating clinics. Disclosures: No relevant conflicts of interest to declare.

Prognostic Significance of Blasts in the Cerebrospinal Fluid Without Pleiocytosis or a Traumatic Lumbar Puncture in Children With Acute Lymphoblastic Leukemia: Experience of the Dutch Childhood Oncology Group

2006 ◽  
Vol 24 (15) ◽  
pp. 2332-2336 ◽  
Author(s):  
D. Maroeska W.M. te Loo ◽  
Willem A. Kamps ◽  
Anna van der Does-van den Berg ◽  
Elisabeth R. van Wering ◽  
Siebold S.N. de Graaf
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lumbar Puncture ◽  
Cox Regression ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Event Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Significant Difference

Purpose To determine the significance of blasts in the CSF without pleiocytosis and a traumatic lumbar puncture in children with acute lymphoblastic leukemia (ALL). Patients and Methods We retrospectively studied a cohort of 526 patients treated in accordance with the virtually identical Dutch protocols ALL-7 and ALL-8. Patients were classified into five groups: CNS1, no blasts in the CSF cytospin; CNS2, blasts present in the cytospin, but leukocytes less than 5/μL; CNS3, blasts present and leukocytes more than 5/μL. Patients with a traumatic lumbar puncture (TLP; > 10 erythrocytes/mL) were classified as TLP+ (blasts present in the cytospin) or TLP− (no blasts). Results Median duration of follow-up was 13.2 years (range, 6.9 to 15.5 years). Event-free survival (EFS) was 72.6% (SE, 2.5%) for CNS1 patients (n = 304), 70.3% (SE, 4.7%) for CNS2 patients (n = 111), and 66.7% (SE, 19%) for CNS3 patients (n = 10; no significant difference in EFS between the groups). EFS was 58% (SE, 7.6%) for TLP+ patients (n = 62) and 82% (SE, 5.2%) for TLP− patients (n = 39; P < .01). Cox regression analysis identified TLP+ status as an independent prognostic factor (risk ratio, 3.5; 95% CI, 1.4 to 8.8; P = .007). Cumulative incidence of CNS relapses was 0.05 and 0.07 in CNS1 and CNS2 patients, respectively (not statistically significant). Conclusion In our experience, the presence of a low number of blasts in the CSF without pleiocytosis has no prognostic significance. In contrast, a traumatic lumbar puncture with blasts in the CSF specimen is associated with an inferior outcome.

Risk Factors in Childhood Acute Lymphoblastic Leukemia: A Single Center Experience in a Developing Country.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4475-4475
Author(s):  
Sema S. Anak ◽  
Leyla Agaoglu ◽  
Arzu Akcay ◽  
Ebru T. Saribeyoglu ◽  
Didem Y. Atay ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
Pediatric All

Abstract Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with the survival rates up to 80–90%, but in high-risk patients the survival rate is still unsatisfactory. The aim of this study is to analyze the pediatric ALL data of a single pediatric university center between 1987–2005 retrospectively to identify risk factors effecting the event free survival (EFS). In order to determine the risk factors possibly effecting the survival, we analyzed gender, age, physical examination findings, blood cell count, FAB morphology, immunophenotyping results, translocations and extramedullary involvement. During the same period, chemotherapy regimens used and response to these protocols were also analyzed. A total of 372 cases [220 male (60%) and 151 female (41%)] were diagnosed and treated in our center between 1987–2005. The age distribution was as follows: 7% patients under 2 years, 68% between 2–10 years, 25% above 10 years of age. At diagnosis, 76% patients had a hemoglobin level <10gr/dl, 56% WBC >10.000/mm3, 74% platelet <100.000/mm3. Primary CNS involvement was positive in 2.5%, mediastinal mass in 8% of all patients. The morphological subtypes were as follows: L1 64%, L2 32%, L3 4%. Immunophenotypic results revealed T ALL in 22%, mature B ALL in 8% and B ALL (common, pre B, proB) in 70%. All patients received CCG modified BFM protocol (80% of all patients) until 1999. Since then high-risk patients were treated with the augmented BFM protocol and L3 patients BFM NHL 95 Protocol, while standard risk patients continued to get the CCG modified BFM protocol. The remission rate at day 33 was 97.8%. Eighty-one patients relapsed (68% patients isolated bone marrow, 16% bone marrow + extramedullary, 9% CNS, 7% testes). According to the univariate analysis of our patient population, the factors negatively effecting the EFS were age <1 year, hepatomegaly >2cm., white blood cell >50.000/mm3 and platelet count <20.000/mm3, L3 FAB morphology, ≥M2 bone marrow status at day 14; CD3, HLADR, CD45 and Tdt negativity. According to the multivariate analysis the most important negative risk factors effecting the EFS were age <1 year, hepatomegaly >2cm. and ≥M2 bone marrow status at day 14 and CD 45 negativity. After a follow up of 72±59 months (1–300 months) 58% of patients are alive & well, 28% were lost to follow up and 14% patients succumbed to death. Overall survival (OS) for 60&120 months follow up were 83%, 83% and event free survival (EFS) 72%, 70% respectively. In conclusion, in ALL patients risk assessment is very important to conduct appropriate therapy. Identifying such factors and implementing risk adapted therapy will improve our treatment results decreasing the toxicity rates in pediatric ALL. Therefore treatment of all ALL patients still remains a challenge.

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.

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 The Outcome of Children With Acute Lymphoblastic Leukemia Without Receiving Sufficient Dose of L-Asparaginase

2020 ◽  
Author(s):  
Gholamreza Bahoush ◽  
Gholamreza Bahoush ◽  
Marzieh Nojomi
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Hypersensitivity Reaction ◽  
Lymphoblastic Leukemia ◽  
Accurate Determination ◽  
Drug Regimen ◽  
Disease Recurrence ◽  
Free Survival ◽  
Complete Treatment

In acute lymphoblastic leukemia (ALL) patients treated with L-asparaginase, discontinuation of the drug occasionally occur due to severe drug complications or resistance, however, due to the high efficacy of this drug in the recovery of patients and the prevention of disease recurrence, resuming the drug regimen is preferred in most patients. What we did in this study was to evaluate and compare the effects of clinical outcomes in the two modes of continuing and discontinuing drug use. In this retrospective cohort study, all children with ALL who had been treated with L-asparaginase during the years 2005 to 2015 were included in the study and categorized into two groups receiving complete treatment regimen (n=160) and those who had to discontinue the drug due to appearing complications (n=9). The rate of relapse and mortality rate was determined and compared across the two groups with a median follow-up time of more than 5 years. 5-yrs Overall survival of all enrolled patients in the groups continued and discontinued was 91.4±2.5% and 71.4±17.1%, respectively (P=0.792). Also, 5-yrs event-free survival of the two groups was 75.8±3.5% and 71.4±17.1%, respectively (P=0.557. Relapse was revealed in 17.5% and 33.3% respectively and mortality in 16.9% and 0.0% (P=0.261). However, the overall prevalence of hypersensitivity reaction to the drug was significantly higher in those patients who discontinued their drug regimen (100% versus 24.4%, P<0.001). Hypersensitivity reaction to drugs may be an important factor in discontinuing L-asparaginase in patients with ALL. The discontinuation of L-asparaginase supplementation due to various complications such as hypersensitivity reactions may be effective in the survival of these patients. However, accurate determination of the effect of discontinuation of this drug on the outcome of children with ALL requires a more comprehensive study with more complicated cases.

scholarly journals Intensified Therapy of Acute Lymphoblastic Leukemia in Adults: Report of the Randomized GRAALL-2005 Clinical Trial

2018 ◽  
Vol 36 (24) ◽  
pp. 2514-2523 ◽  
Author(s):  
Françoise Huguet ◽  
Sylvie Chevret ◽  
Thibaut Leguay ◽  
Xavier Thomas ◽  
Nicolas Boissel ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Standard Dose ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Treatment Phase ◽  
Free Survival ◽  
Treatment Tolerance ◽  
To Receive

Purpose To evaluate randomly the role of hyperfractionated cyclophosphamide (hyper-C) dose intensification in adults with newly diagnosed Philadelphia chromosome–negative acute lymphoblastic leukemia treated with a pediatric-inspired protocol and to determine the upper age limit for treatment tolerability in this context. Patients and Methods A total of 787 evaluable patients (B/T lineage, 525 and 262, respectively; median age, 36.1 years) were randomly assigned to receive a standard dose of cyclophosphamide or hyper-C during first induction and late intensification. Compliance with chemotherapy was assessed by median doses actually received during each treatment phase by patients potentially exposed to the full planned doses. Results Overall complete remission (CR) rate was 91.9%. With a median follow-up of 5.2 years, the 5-year rate of event-free survival (EFS) and overall survival (OS) was 52.2% (95% CI, 48.5% to 55.7%) and 58.5% (95% CI, 54.8% to 61.9%), respectively. Randomization to the hyper-C arm did not increase the CR rate or prolong EFS or OS. As a result of worse treatment tolerance, advanced age continuously affected CR rate, EFS, and OS, with 55 years as the best age cutoff. At 5 years, EFS was 55.7% (95% CI, 51.8% to 59.4%) for patients younger than 55 years of age versus 25.8% (95% CI, 19.9% to 35.6%) in older patients (hazard ratio, 2.16; P < .001). Patients ≥ 55 years of age, in whom a lower compliance to the whole planned chemotherapy was observed, benefited significantly from hyper-C, whereas younger patients did not. Conclusion No significant benefit was associated with the introduction of a hyper-C sequence into a frontline pediatric-like adult acute lymphoblastic leukemia therapy. Overall, tolerability of an intensive pediatric-derived treatment was poor in patients ≥ 55 years of age.

scholarly journals Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3122-3133 ◽  
Author(s):  
A Reiter ◽  
M Schrappe ◽  
WD Ludwig ◽  
W Hiddemann ◽  
S Sauter ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Multicenter Trial ◽  
Low Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
To Receive

Abstract In trial ALL-BFM 86, the largest multicenter trial of the Berlin- Frankfurt-Munster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight- drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD- cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety- eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

Allogeneic bone marrow transplantation for acute lymphoblastic leukemia in remission: prolonged survival associated with acute graft-versus-host disease.

1987 ◽  
Vol 5 (9) ◽  
pp. 1348-1355 ◽  
Author(s):  
D J Weisdorf ◽  
M E Nesbit ◽  
N K Ramsay ◽  
W G Woods ◽  
A I Goldman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
High Risk ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Maintenance Chemotherapy ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Acute Graft

Forty remission patients with high-risk acute lymphoblastic leukemia (ALL) underwent matched allogenic bone marrow transplantation (BMT) following preparation with cyclophosphamide and fractionated total body irradiation (TBI). As of March 1987, the median follow-up is more than 3 1/2 years. Thirteen patients are alive (11 relapse free) between 2 and 4 1/2 years post-BMT. Neither age, sex, remission number, prior extramedullary leukemia, nor WBC at diagnosis of ALL was statistically significant as a predictor of relapse-free survival. The development of acute graft-v-host disease (GVHD) in 17 patients was found, with time-dependent Cox regression analysis, to be associated with a significant reduction in post-BMT relapse risk (P = .04) and improved disease-free survival (P = .11). A prospective, randomized trial of maintenance chemotherapy with oral methotrexate and mercaptopurine did not demonstrate improvement in relapse risk or survival for those assigned maintenance chemotherapy (P = .7). These results suggest that allogeneic BMT can result in extended relapse-free survival for some patients with high-risk ALL. More effective preparative chemoradiotherapy and exploitation of the apparent graft-v-leukemia effect may be useful in future trials.

Secondary brain tumors in children treated for acute lymphoblastic leukemia at St Jude Children's Research Hospital.

1998 ◽  
Vol 16 (12) ◽  
pp. 3761-3767 ◽  
Author(s):  
A W Walter ◽  
M L Hancock ◽  
C H Pui ◽  
M M Hudson ◽  
J S Ochs ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Brain Tumors ◽  
Lymphoblastic Leukemia ◽  
Low Grade ◽  
High Grade ◽  
Research Hospital ◽  
Dose Dependent

PURPOSE To evaluate the incidence of and potential risk factors for second malignant neoplasms of the brain following treatment for childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS The study population consisted of 1,612 consecutively enrolled protocol patients treated on sequential institutional protocols for newly diagnosed ALL at St Jude Children's Research Hospital (SJCRH) between 1967 and 1988. The median follow-up duration is 15.9 years (range, 5.5 to 29.9 y). RESULTS The cumulative incidence of brain tumors at 20 years is 1.39% (95% confidence interval [CI], 0.63% to 2.15%). Twenty-two brain tumors (10 high-grade gliomas, one low-grade glioma, and 11 meningiomas) were diagnosed among 21 patients after a median latency of 12.6 years (high-grade gliomas, 9.1 years; meningiomas, 19 years). Tumor type was linked to outcome, with patients who developed high-grade tumors doing poorly and those who developed low-grade tumors doing well. Risk factors for developing any secondary brain tumor included the presence of CNS leukemia at diagnosis, treatment on Total X therapy, and the use of cranial irradiation, which was dose-dependent. Age less than 6 years was associated with an increased risk of developing a high-grade glioma. CONCLUSION This single-institution study, with a high rate of long-term data capture, demonstrated that brain tumors are a rare, late complication of therapy for ALL. We report many more low-grade tumors than others probably because of exhaustive long-term follow-up evaluation. The importance of limiting cranial radiation is underscored by the dose-dependent tumorigenic effect of radiation therapy seen in this study.

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