Therapy-induced Acute Lymphocytic Leukemia with the 11q23 Translocation: 2 Cases and a Review of the Literature

Case Report

J Stem Cell Res Transplant. 2014;1(2): 1010.

Therapy-induced Acute Lymphocytic Leukemia with the 11q23 Translocation: 2 Cases and a Review of the Literature

Syed M. Rizvi1*, Monica Joshi1, Mala Talekar2, David F. Claxton1, Christopher W. Ehmann1, Harold A. Harvey1 and Joseph J. Drabick1

1The Hematology-Oncology Division, University Drive, USA

2The Hematology-Oncology Division, Penn State Children’s Hospital, USA

*Corresponding author: Dr. Syed Rizvi at Hematology-Oncology Division, 500 University Drive, PO Box 850, Hershey PA 17033-0850, USA

Received: September 03, 2014; Accepted: September 27, 2014; Published: September 29, 2014


We report two cases of therapy-induced ALL (t-ALL) with the 11q23 translocation (Mixed Lineage Leukemia or MLL rearrangement). Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are well known to occur in patients who had previously received topoisomerase II inhibitors or alkylating agents for the treatment of a prior malignancy. t- ALL, however, is a rare entity. Similar to therapy- induced AML (t-AML) or MDS; t-ALL can also be associated with the11q23 translocation. This translocation typically occurs in t-AML secondary to prior DNA topoisomerase II inhibitor therapy. We present two uniquecases of t-ALL along with the literature review of 30 previously reported t-ALL cases associated with the 11q23 translocation. A balanced translocation at the 11q23 region was observed in most cases as in our review. The MLL gene at locus 11q23 was observed to have a break point in the majority of analyzed cases at a site similar to t-AML. All the t-ALL cases reviewedwith the 11q23 translocation were secondary to prior topoisomerase II inhibitor therapy. The diagnosis of t-ALL was made at a median time point of 19 months from prior therapy. t-ALL, similar to t-AML with an 11q23 translocation, is associated with a poor prognosis. These patients should be considered for allogeneic stem cell transplantation in first complete remission. This therapeutic approach may improve the long term overall survival. However, given the dearth of clinical trials in this select population, further clinical studies need to be done to validate this approach.

Keywords: ALL; t-ALL; 11q23 Translocation; Bone marrow transplant; Secondary leukemia


AML (acute myeloid leukemia) occurs at an increased frequency in patients previously treated with alkylating agents and topoisomerase II inhibitors [1]. Leukemia secondary to previous use of alkylating agents is most commonly associated with the rearrangements of chromosome 5 and/or chromosome 7 [1,2]. However, in the 1990s, a small subset of AML was reported by Pedersen-Bjergaard et al. [3,4] along with several other groups [5-10] that had a karyotype specific for de novo AML. Most of these patients were reported to have a balanced translocation between the 11q23 region and another chromosome and majority of them had received topoisomerase II directed agent (i.e., the epipodophillotoxins, VP 16 or VM 26 and, to a lesser extent, anthracyclines or their derivatives) for their previous cancers [3,4,9-11].

Interestingly, the occurrence of ALL ( acute lymphoid leukemia ) secondary to either prior chemotherapy or radiotherapy is very rare [11]. In a pediatric case series of secondary acute leukemias, only 6 % were found to be therapy related ALL ( t-ALL ) [12]. Andersan et al. [13] reviewed 23 cases of chemotherapy related ALL since 1992, all of which hada balanced 11q23 translocation. All of these patients had received prior topoisomerase II inhibitors [13]. Auxenfants et al. [11] and Pui et al. [9] reported similar associations in their reviews. DNA topoisomerase II therapy is recognized to be strongly associated with the occurrence of balanced translocations of 11q23 and chimeric rearrangements of the MLL gene in t-AML [14]. This is very likely to be the cause of similar genetic anomalies in t-ALL [13].

In this article, we report two observed cases of secondary ALL with t(4;11)(q21;q23) in our institution along with literature review of 30 previously published cases.

Case 1

A 68 year old gentleman presented with a left lung mass that had been incidentally picked up on a routine chest x-ray in March 2007. He was diagnosed with small cell lung cancer and was treated with cisplatin and etoposide for 4 cycles. He also received concurrent 45 Gy in 30 fractions to the mediastinum with a curative intent. He had a complete response to chemo-radiation and went on the receive prophylactic cranial radiation (36 Gy in 18 fractions). He was in complete remission until January 2009, when he presented with fever, malaise and had a marked leukocytosis on laboratory evaluation. His white blood cell count was 288.5 K/uL. He also had mild anemia with hemoglobin at 12.1g/dl and thrombocytopenia with platelets of 39 K/uL. Bone marrow biopsy showed a hyper cellular marrow with lymphoblastic predominance (80 % of bone marrow). The blasts expressed CD 19, HLA-DR, CD22 and TdT andCD10 was found to be negative. The morphological and phenotypic appearance of the marrow was consistent with precursor B cell ALL. Further genetic studies demonstrated stable translocation, t (4, 11) with the MLL gene re-arrangementin 91 % of nuclei. He was treated with multi-agent induction chemotherapy per Larsen protocol (cyclophosphamide, daunorubicin, vincristine, prednisone, l-asparginase) and an allogeneic hematopoietic transplant was being considered. He achieved a complete morphologic and molecular remission without any evidence of t (4, 11) translocation on FISH analysis after Phase 1. Unfortunately, he relapsed shortly thereafter and decided to pursue comfort measures only.

Case 2

A 31 year old gentleman presented in August of 2007 with a right medial thigh mass which he had noticed while playing soft ball. Subsequently, he was diagnosed to have a high grade soft tissue sarcoma on excisional biopsy. The specimen had mixed features of an undifferentiated high grade pleomorphic sarcoma and myxoidliposarcoma. He received neoadjuvant chemotherapy with MAI (doxorubicin, total dose was 200 mg per meter squared) and one cycle of cisplatin. He later underwent a limb preserving surgery post chemotherapy. Surgical pathology revealed microscopic evidence of disease at the surgical margins and hence he received adjuvant external beam radiation of 60 Gy to the tumor bed with a boost to the scar of a total of 66 Gy. He had a delayed bone marrow recovery and by fall of 2008, he had developed persistent cytopenias raising the concern for MDS and therapy related leukemia. A bone marrow was performed in November of 2008 which showed marked hypoplasia. Circulating blasts were present in peripheral blood and further testing revealed morphological and phenotypical features consistent with pre-B lymphoblastic leukemia. The lymphoblasts expressed CD19, CD34, TdT, HLA-DR, but they did not express CD10. Cytogenetic studies performed at that time showed the presence of a balanced translocation t(4,11) in 12.6 % of nuclei. The break point on chromosome 11 was at band q23-MLL gene. He received mulitagent induction chemotherapy in November of 2008 per Larsen protocol (cyclophosphamide, daunorubicin, vincristine, prednisone, l-asparginase). A bone marrow biopsy performed on 1/9/2009 showed no morphologic evidence of leukemia consistent with complete hematologic remission with a negative FISH for MLL rearrangement. He received some additional chemotherapy and CNS prophylactic chemotherapy to maintain remission while awaiting a potential allogeneic stem cell donor. He underwent a non-myeloablative allogeneic stem cell transplant from a matched unrelated donor in June 2009 and he continues to be in remission to date with excellent quality of life (Table 1).

Citation: Rizvi SM, Joshi M, Talekar M, Claxton DF, Ehmann CW, et al. Therapy-induced Acute Lymphocytic Leukemia with the 11q23 Translocation: 2 Cases and a Review of the Literature. J Stem Cell Res Transplant. 2014;1(2): 1010. ISSN:2381-9065