Chronic Myeloid Leukemia Following Treatment for Primary Neoplasms or Other Medical Conditions

A Report of 21 Cases and Review of the Literature

Lian-He Yang, MD, PhD; Pu Su, MD, PhD; Catherine Luedke, MD; Chuanyi Mark Lu, MD; Abner Louissaint Jr, MD, PhD; Chad M. McCall, MD, PhD; Sarah Rapisardo, PhD; Bethany Vallangeon, MD; Endi Wang, MD, PhD

Disclosures

Am J Clin Pathol. 2018;150(3):246-258. 

In This Article

Results

Clinical Findings

The clinicopathologic features of the 21 cases are summarized in Table 1. Of 21 patients, eight were female and 13 were male. The median age at diagnosis of the primary condition was 55.3 years with range of 35 to 87.2 (mean = 55.8 ± 13.7 years). The median age at diagnosis of CML was 64 years with range of 38 to 88 (mean = 62 ± 13.2 years). Primary diagnoses included lymphoid neoplasms (n = 7), breast carcinoma (n = 3), lung carcinoma (n = 2), bladder carcinoma (n = 1), thyroid carcinoma (n = 1), cholangiocarcinoma (n = 1), prostatic carcinoma (n = 1), colorectal carcinoma (n = 1), carcinoma of the ampulla of Vater (n = 1), metastatic pheochromocytoma (n = 1), and organ failure requiring solid organ transplant (n = 2). Therapy for the primary conditions included combinations of chemotherapy/radiotherapy in nine cases, radiotherapy alone or radiotherapy plus rituximab in four cases, chemotherapy alone in five cases, solid organ transplantation followed by immunosuppression in two cases, and tumor excision in the remaining case. The interval between primary and secondary diagnoses ranged from 10 to 180 months with a median of 71 months (mean = 74.4 ± 49.9 months).

Pathologic Features

Of 17 cases with clinical information available, all patients presented with leukocytosis. In addition, five patients presented with splenomegaly, two patients with fatigue, one patient with anemia, and another patient with thrombocytosis. All 21 cases demonstrated pathologic features characteristic of CML, including BCR/ABL1 fusion detected by fluorescence in situ hybridization (FISH) and/or molecular diagnostics, and/or Philadelphia chromosome, t(9;22)(q34;q11.2), detected by conventional cytogenetic studies. Eighteen cases had chromosomal analyses performed, of which 16 demonstrated Philadelphia chromosome without other additional aberrations. Two cases showed a single translocation, t(1;16) or t(1;17), respectively, in addition to Philadelphia chromosome (cases 2 and 13). Interphase FISH analysis was performed in 13 cases, confirming the presence of the BCR/ABL1 gene fusion, including three cases in which chromosomal analysis was not performed or failed. Of the 17 cases with clinicopathologic information available, all demonstrated features consistent with CML in chronic phase. All but one patient had treatment and follow-up information available. Of these, all 20 patients were treated with imatinib, nilotinib, or dasatinib, and 18 were alive with follow-up ranging from 1 to 113 months (median = 22 months). These included five with complete molecular responses, 12 with partial molecular responses, and one with evolution to B-lymphoblastic leukemia (B-ALL) at 6 months after treatment. Two patients (cases 2 and 3) died at 5 and 27 months after diagnosis, respectively, but a medical record review showed evidence of death due to dissemination of the patient's primary malignancy rather than CML, which was in hematologic remission. Survival analysis could not be performed due to lack of disease-specific terminal events in our series.

Literature Review

We reviewed the literature and collected 109 cases of therapy-related CML reported since 1983 Table 2.[4–20,22–36,38–47,51–62,64,66–71,75–77,79,81,82,84,87–90,92,93,95] These cases were analyzed and compared with our present cases Table 3. Of 103 cases with information available, 60 were males and 43 were females, with a sex ratio of 1.4, a number similar to that of our series (sex ratio of 1.6). The median age at diagnosis of CML for the pooled reported cases was 53.5 years with a range of 4 to 82 years, in comparison to 64 years (range = 38–88 years) in our series. The primary conditions included lymphoma in 30 cases (27.5%), non-CML leukemia in 22 cases (20.2%), gastrointestinal carcinoma in 14 cases (12.8%), breast carcinoma in nine cases (8.3%), thoracic neoplasm in seven (6.4%) cases, thyroid carcinoma in six cases (5.5%), genitourinary neoplasm in nine cases (8.3%), soft tissue sarcoma in four cases (3.7%), tumor of the female reproductive system in three cases (2.8%), and other malignancies/conditions in five (4.6%) cases. The median interval between the diagnosis of the patient's primary neoplasm/condition and CML was 60 months with a range of 8 to 396 months, in contrast to 71 months (range = 10–180 months) in our series. While more than 93.6% of the patients presented as CML in chronic phase, accelerated phase and blast crisis comprised 3.9% and 2.6% of the total reported cases, respectively. Of the cases with cytogenetic data documented, 83.5% demonstrated isolated Philadelphia chromosome, in comparison with 88.9% in our series. The remaining reported cases showed additional, random aberrations, except for two cases with monosomy 7 and an additional case with −7/–5q. Therapy and follow-up were limited. Of 109 cases, 80 (73.4%) were treated with imatinib or its derivatives, at least during part of their disease course. Of 78 cases with a median follow-up of 19.5 months (range = 0.5–216 months), 60.3% of the patients were alive at the time of case publication. Of 29 patients who were reported to be dead, 75.9% (22/29) died of disease progression, 13.8% (4/29) died of non-CML cause, and 10.3% (3/29) had no cause of death implicitly indicated.

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