Cumulative Incidence of Secondary Neoplasms as a First Event After Childhood Acute Lymphoblastic Leukemia

Hijiya, Nobuko; Hudson, Melissa M.; Lensing, Shelly; Zacher, Margie; Onciu, Mihaela; Behm, FG; Razzouk, Bassem I.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Sandlund, John T.; Rivera, Gaston K.; Evans, William E.; Relling, Mary V.; Pui, Ching Hon

doi:10.1001/jama.297.11.1207

Cited by 282 publications

(280 citation statements)

References 33 publications

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“…16 The findings of Hijiya et al agree with those of others reporting poor prognosis for childhood cancer survivors with secondary AML. 6,16,21 In contrast, the German Cooperative Group 22 and the Italian Group for Adult Hematologic Diseases 23 showed that outcomes of adult survivors with secondary AML are not worse than those of de novo AML when adjusted for cytogenetic features.…”

Section: Discussionmentioning

confidence: 99%

“…Hijiya et al 21 reported 37 cases of secondary AML among 123 patients who developed secondary malignancies after treatment for childhood ALL; the 5-year survival of the group with secondary AML was poorer (18%) than of those with other types of secondary hematological malignancies. Another study by Hijiya et al 17 comparing outcomes of ALL, AML, and secondary AML using SEER data showed significantly lower 5-year survival (23.7%; P < .001) for children with secondary AML compared with those with de novo AML (53.2%).…”

Section: Discussionmentioning

confidence: 99%

“…25 In 14 ALL consecutive studies reported by St. Jude, only 2 of 2304 patients with primary ALL were later diagnosed with secondary ALL. 21 In most cases, these leukemias were misdiagnosed as recurrences of primary ALL, especially before molecular detection of immunoglobulin and T-cell receptor rearrangements was available. Zuna et al 24 showed that 0.5% to 1.5% of 366 cases of recurrent ALL were actually secondary ALL and proposed diagnostic criteria for secondary ALL that mandate molecular evidence of a new leukemic clone emergence, plus immunophenotypic and/or cytogenetic shift and/or fusion gene gain or loss.…”

Section: Discussionmentioning

confidence: 99%

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Secondary hematopoietic malignancies in survivors of childhood cancer

Rihani

Bazzeh

Faqih

et al. 2010

Cancer

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BACKGROUND: Studying secondary hematological malignancies in a large cohort of patients can help predict risks and trends associated with current therapies. METHODS: The authors analyzed data from the Surveillance, Epidemiology, and End Resultsecondary 9 (SEER-9) database on patients with a primary malignancy (diagnosed before the age of 20 years) between 1973 and 2005 who developed a secondary hematological malignancy. Primary cancer and histological subtype, incidence, risk factors, outcomes, and changes in risk patterns of secondary hematological malignancies were analyzed for 1973 to 1985, 1986 to 1995, and 1996 to 2005. Standardized incidence ratios (SIRs) of observed to expected cancers were calculated. RESULTS: Of 34,867 patients with a histology-confirmed primary malignancy, 111 developed secondary hematological malignancies (median, 44 months). Lymphoma was the commonest primary cancer (n ¼ 47). The main histological subtype of secondary hematological malignancy was acute myeloid leukemia (AML) (49%), which had the shortest median latency time and the worst 5-year survival (18% AE 5.3%; P ¼.044). Secondary Hodgkin lymphoma had the best 5-year survival (83% AE 15%). The 5-year overall survival for patients with secondary hematological malignancies was 31% AE 4.7%. The risk of secondary AML steadily increased from 1986 to 2005, whereas SIRs for acute lymphoblastic leukemia did not change over time. Non-Hodgkin lymphoma, the second most common secondary hematological malignancy, occurred at a median of 112 months, and its risk steadily increased over time periods. CONCLUSIONS: Childhood cancer survivors are at increased risk of developing secondary hematological malignancies, particularly secondary AML. This risk has continued to rise even in recent years, emphasizing the need to study other factors contributing to secondary hematological malignancies and closely monitor these patients. Cancer 2010;116:4385-94.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Secondary hematopoietic malignancies in survivors of childhood cancer

Rihani

Bazzeh

Faqih

et al. 2010

Cancer

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“…Most study groups reinforce CNS-directed therapy in patients with CNS-positive using cranial irradiation and addition of IT chemotherapy, as they are thought to be at a greater risk for CNS and other relapse [7]. The disadvantage of cranial irradiation has been recognized [4][5][6]. Further, IT chemotherapy is accompanied by neurotoxicities [21,22].…”

Section: Discussionmentioning

confidence: 99%

“…However, administering CNS-directed therapy always results in a dilemma between sufficient intensity and treatmentrelated toxicity. Especially, the use of pCRT should be avoided because of its substantial risk for late complications such as second malignancies, endocrinopathies, neurocognitive dysfunctions, and neurotoxic effects [4][5][6]. On the other hand, CNS relapse still occurs in 2-5% of children with ALL and remains to be a treatment obstacle [7].…”

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confidence: 99%

The utility of performing the initial lumbar puncture on day 8 in remission induction therapy for childhood acute lymphoblastic leukemia: TCCSG L99‐15 study

Hasegawa

Manabe

Ohara

et al. 2011

Pediatric Blood & Cancer

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INTRODUCTIONThe long-term cure rate in childhood acute lymphoblastic leukemia (ALL) is as high as 80% [1,2], and this is largely attributable to sufficient central nervous system (CNS)-directed therapy, such as prophylactic cranial irradiation (pCRT) and intrathecal chemotherapy (IT) [3]. However, administering CNS-directed therapy always results in a dilemma between sufficient intensity and treatmentrelated toxicity. Especially, the use of pCRT should be avoided because of its substantial risk for late complications such as second malignancies, endocrinopathies, neurocognitive dysfunctions, and neurotoxic effects [4][5][6]. On the other hand, CNS relapse still occurs in 2-5% of children with ALL and remains to be a treatment obstacle [7]. Therefore, proper assessment of risk factors for CNS relapse is required.Risk factors for CNS relapse include a T-cell immunophenotype, hyperleukocytosis, specific genetic alterations such as t(9;22) and t(4;11), and the presence of CNS involvement [7]. The prognostic significance of the presence of leukemic blasts in the cerebrospinal fluid (CSF) without pleocytosis, referred to as CNS-2, has varied in clinical trials and is heavily dependent on the effectiveness of systemic and CNS-directed therapy [8][9][10][11]. By contrast, traumatic lumbar puncture with leukemic blasts (TLPþ) adversely affects the outcome of patients with ALL as well as overt CNS leukemia [2,9-11]. Though controversy over whether TLPþ is an iatrogenic event or intrinsically inevitable status still exists, clinicians should pay attention to keep the rate of TLPþ to a minimum.To overcome the problem concerning TLPþ, the Tokyo Children's Cancer Study Group (TCCSG) adopted a strategy to postpone the initial lumbar puncture (LP) and IT until 7 days after prednisolone (PSL) monotherapy in the L89-12 study in order to decrease circulating leukemic blasts substantially before the initial LP/IT [12]. This strategy yielded a significant reduction of TLPþ [12], but the net effect on the outcome was not clarified because over 80% of the patients received cranial irradiation in the L89-12 study [12,13]. We hypothesized that deferring the initial LP/ITuntil day 8 in remission induction therapy could reduce the frequency of cases with TLPþ without compromising outcome, even if the indication for pCRT is restricted. Here, we report the results of the L99-15 study adopting the day 8 LP/IT strategy and restricting the indication for pCRT.

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Childhood Acute Lymphoblastic Leukaemia

Campana¹,

Pui²

2005

Postgraduate Haematology

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The cure rate for childhood acute lymphoblastic leukemia (ALL) now exceeds 70%. This success has been achieved in part by improvements in the biologic characterization of newly diagnosed patients. Modern treatment protocols rely on this information to tailor therapy to a patient's risk of relapse. Patients with favorable genetic features, such as hyperdiploidy or the TEL-AML1 fusion, can be treated with conventional antimetabolite-based therapy to minimize long-term side effects. By contrast, extremely high-risk patients, such as infants with MLL gene rearrangements and cases with BCR-ABL fusion and poor early response, are candidates for allogeneic hematopoietic stem cell transplantation in first remission. Future areas of research include the identification of new genetic subgroups of ALL and the development of novel therapies.

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Cumulative Incidence of Secondary Neoplasms as a First Event After Childhood Acute Lymphoblastic Leukemia

Cited by 282 publications

References 33 publications

Secondary hematopoietic malignancies in survivors of childhood cancer

Secondary hematopoietic malignancies in survivors of childhood cancer

The utility of performing the initial lumbar puncture on day 8 in remission induction therapy for childhood acute lymphoblastic leukemia: TCCSG L99‐15 study

Childhood Acute Lymphoblastic Leukaemia

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