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Editorials
Table 1. Main studies on therapy-related acute lymphoblastic leukemia (t-ALL) and secondary acute lymphoblastic leukemia (s-ALL).
Author (year)
Pagano (1999)
N t-ALL/ s-ALL
21
Frequency
2.3%
NR
9.6%
6.9%
4%
1.9%
5.3%
3%
6.6%
9.1%
Age (median, [range]), years
58 (33-78)
65 (30-86)
51 (17-75)
55 (3.3-87) t-ALL: 52 (3.3-76) s-ALL: 75 (23-87)
62 (21-90)
t-ALL: 55 (20-78) s-ALL: 65 (25-72)
NR
NR
55 (23-85)
Shivakumar 1012 (2008)
Most frequent antecedent solid
tumor
Breast
Breast
Breast
Breast
Breast
Breast
Breast
Breast
Breast Prostate
Breast
Most frequent antecedent hematologic
cancer
Hodgkin’s lymphoma
Lymphoma
Lymphoma
Lymphoma
Lymphoma
Lymphoma
Lymphoma
Lymphoma
Lymphoproliferative neoplasms Myeloid neoplasms
Lymphoproliferative neoplasms
Interval prior malignancy-ALL (median [ range]),
months
27 (4-170)
<18 yr: 36 (3-240) 18-59 yr: 26 (6-192) ≥60 yr: 22 (4-168)
t-ALL: 36 (6-216) s-ALL: 144 (7-420)
48 (5-360)
64 (2-336) t-ALL: 72 (9-336) s-ALL: 48 (2-336)
60 (12-198)
t-ALL: 37 (7-333) s-ALL: 84 (29-219)
67 (2.6-277)
60 (2-473)
82 (10-608)
Main cytogenetic findings1
t(9;22) 11q23
11q23 t(9;22) Complex karyotype
11q23, t(9;22) -5, -7 -17, -17p Hypodiploid
11q23
t(9;22)
t(9,22) Hypodiploid -7/7p- 11q23
NR
CR
12 (57%)
40/72 (56%)
t-ALL: 18/30 (60%) s-ALL: 10/14 (71%)
17/21 (81%)
25 (86%)
NR
HSCT OS/EFS in CR1
NR OS: median 5 months
14/40 OS: median 6-7 months
NR EFS: 13% (3-yr)
5/18 OS: 37% (3-yr)
6/25 OS: 25% (2-yr)
NR OS: 6.8% (5-yr)
3/21 OS:
t-ALL: 71% (3-yr)
s-ALL: 38% (3-yr)
NR NR4
NR OS: 10% (5-yr)
49/79 OS: 46% (2-yr)
Tang (2012)
44 30/14
Abdulwahab 23
(2012) (all t-ALL)
Ganzel 32 (2015) 23/9
Giri3 79
(2015)
Kelleher 24 (2016) 16/8
Rosenberg3 371
t(9;22) Hypodiploidy (94%)
11q23 s-ALL: 6/8 (75%)
NR NR
NR NR
t(9;22) 79/93 (85%) 11q23
-5/5q-/-7/7q-
Complex karyotype
t-ALL: 15/16
(2017)
Swaika3 (2018)
Aldoss (2018)
184/187 772
93 (all t-ALL)
1In order of frequency; 2Seven own patients and 94 collected from the literature. 3Epidemiologic study. 4Patients with t-ALL were at significantly increased risk of death compared to de novo ALL patients. NR: not reported; CR: complete remission; HSCT: hematopoietic stem cell transplantation; CR1: first complete remission; OS: overall survival; EFS: event-free survival.
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hematologic cancer, and the same reasons for breast can- cer could be applied to explain this high frequency of t- ALL. In studies including large series, patients with a pre- vious primary hematological malignancy had a higher risk for s-ALL or t-ALL as compared to solid organ neo- plasms.12 The latency from prior diagnosis of cancer to t- ALL varies among the case series, but in general it tends to be shorter than in s-ALL and slightly longer than in t- AML or in t-MDS. Among t-ALL cases, those with KMT2A rearrangements show a shorter time interval and those with a Ph-positive rearrangement show a longer interval between the previous cancer and the develop- ment of leukemia.1,2-14,16
Regarding the therapy of t-ALL patients, there is con- cern about the possible impact of previous exposure to chemotherapy and/or to radiotherapy on the toxicity of the chemotherapeutic agents given in induction and con- solidation. However, the tolerability and the treatment- related mortality were similar to that observed in de novo ALL in most studies.1 In some studies, the CR rate was
similar, but in others it was lower than in newly diag- nosed ALL cases (Table 1). Considering the retrospective nature of most of the studies and the long period of patient recruitment, data regarding the measurable (mini- mal) residual disease (MRD) clearance are very limited. As the selection to proceed to alloHSCT was not based on MRD levels, the perception of their poor prognosis (similar to what occurs in t-AML and t-MDS) explains the higher use of transplantation in these patients in some series.1,15 Given the advanced age of most t-ALL patients, reduced-intensity regimens are more frequently used for conditioning. The transplant-related mortality and the rate of relapse after transplantation have shown to be similar to those of de novo ALL in some studies.1 However, when considering the transplanted and non-transplanted cases together, the survival of t-ALL patients is poorer than that observed in de novo ALL (Table 1), this difference being especially evident in the group of non-transplanted cases.1 Population-based studies also have shown a poor- er outcome for ALL patients with antecedent neopla-
haematologica | 2018; 103(10)