Myeloid neoplasms in the setting of chronic lymphocytic leukaemia/chronic lymphocytic leukaemia-like disease: a clinicopathological study of 66 cases comparing cases with prior history of treatment to those without.

AIMS: Myeloid neoplasms occur in the setting of chronic lymphocytic leukaemia (CLL)/CLL-like disease. The underlying pathogenesis has not been elucidated. METHODS: Retrospectively analysed 66 cases of myeloid neoplasms in patients with CLL/CLL-like disease. RESULTS: Of these, 33 patients (group 1) had received treatment for CLL/CLL-like disease, while the other 33 patients (group 2) had either concurrent diagnoses or untreated CLL/CLL-like disease before identifying myeloid neoplasms. The two categories had distinct features in clinical presentation, spectrum of myeloid neoplasm, morphology, cytogenetic profile and clinical outcome. Compared with group 2, group 1 demonstrated a younger age at the diagnosis of myeloid neoplasm (median, 65 vs 71 years), a higher fraction of myelodysplastic syndrome (64% vs 36%; OR: 3.1; p<0.05), a higher rate of adverse unbalanced cytogenetic abnormalities, including complex changes, -5/5q- and/or -7/7q- (83% vs 28%; OR: 13.1; p<0.001) and a shorter overall survival (median, 12 vs 44 months; p<0.05). CONCLUSIONS: Myeloid neoplasm in the setting of CLL/CLL-like disease can be divided into two categories, one with prior treatment for CLL/CLL-like disease and the other without. CLL-type treatment may accelerate myeloid leukaemogenesis. The risk is estimated to be 13-fold higher in patients with treatment than those without. The causative agent could be attributed to fludarabine in combination with alkylators, based on the latency of myeloid leukaemogenesis and the cytogenetic profile.

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

OBJECTIVES: Therapy-related chronic myeloid leukemia (CML) has been reported, but its clinical presentation and pathologic features have not yet been well characterized. METHODS: Twenty-one cases of CML following treatment for primary diseases were collected and retrospectively analyzed. RESULTS: The clinical presentation, pathologic features, and cytogenetic profile were similar to de novo CML. In particular, those with an isolated Philadelphia chromosome constituted 88.9% of our cases, and additional aberrations characteristic of therapy-related acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) were not identified in this study. The patients responded to imatinib/derivatives and survived with limited follow-up. CONCLUSIONS: Therapy-related CML has a clinical presentation, pathologic features, and cytogenetic profile akin to de novo CML. Absence of additional significant aberrations seems to suggest a pathogenesis different from therapy-related AML/MDS. Therapy-related CML exhibits a robust therapeutic response to imatinib/derivatives and favorable clinical outcomes similar to de novo CML.

Myeloid Neoplasms Following Solid Organ Transplantation: Clinicopathologic Studies of 23 Cases.

OBJECTIVES: Myeloid neoplasms (MNs) after solid organ transplant are rare, and their clinicopathologic features have not been well characterized. METHODS: We retrospectively analyzed 23 such cases. RESULTS: The ages ranged from 2 to 76 years, with a median of 59 years at the diagnosis. The median interval between the transplant and diagnosis was 56 months (range, 8-384 months). The transplanted organs included liver in five, kidney in six, lung in five, heart in six, and heart/lung in one case(s). The types of MN included acute myeloid leukemia (AML) in 12, myelodysplastic syndrome (MDS) in five, chronic myelogenous leukemia (CML) in four, and myeloproliferative neoplasms (MPNs) in two cases. Cytogenetics demonstrated clonal abnormalities in 18 (78.3%) cases, including unbalanced changes in 10 (55.6%), Philadelphia chromosome in four (22.2%), and other balanced aberrations in four (22.2%) cases. Thirteen (56.5%) patients died, with an estimated median survival of 9 months. With disease stratification, AML and MDS have short median survivals (3.5 and 7 months, respectively), with an initial precipitous decline of the survival curve. CONCLUSIONS: Posttransplant MNs have a latency period between that seen in AML/MDS related to alkylators and that associated with topoisomerase II inhibitors. The cytogenetic profile suggests a mutagenic effect on leukemogenesis. The clinical outcome for AML/MDS is dismal, with death occurring at an early phase of treatment.

The Challenges of Precision Medicine and New Advances in Molecular Diagnostic Testing in Hematolymphoid Malignancies: Impact on the VHA.

The Hematopathology Molecular Genetics subcommittee presents recommendations for molecular diagnostic testing in acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndrome, and lymphomas and for the development of an interfacility consultation service.

Donor cell-derived leukemias/myelodysplastic neoplasms in allogeneic hematopoietic stem cell transplant recipients: a clinicopathologic study of 10 cases and a comprehensive review of the literature.

We report 10 cases of donor cell leukemia (DCL). All cases except the case of chronic lymphocytic leukemia had anemia, neutropenia, and/or thrombocytopenia when DCL was diagnosed. Eight cases with sex-mismatched hematopoietic stem cell transplant (HCT) showed donor gonosomal complements, suggesting DCL. Clonal cytogenetic abnormalities were detected in 8 cases: 6 were monosomy 7/del(7q). In all 10 cases, engraftment studies confirmed donor cell origin. Retrospective fluorescence in situ hybridization in archived donor cells in 4 cases showed a low level of abnormalities in 2. Of 7 patients with clinical follow-up of 5 months or more, 1 (with acute myeloid leukemia) died of disease; 6 are alive, including 1 with myelodysplastic syndrome with spontaneous remission. Similar to reported cases, we found disproportional sex-mismatched HCTs, suggesting probable underdetection of DCL in sex-matched HCTs. The latency between HCT and DCL ranged from 1 to 193 months (median, 24 months), in keeping with the literature. Analyzing our cases, pooled with reported cases, with survival models showed much shorter latency for malignancy as primary disease, for T-cell large granular lymphocyte leukemia as type of DCL, and for umbilical cord blood as stem cell source.

Pseudo-Pelger-Huët anomaly induced by medications: a clinicopathologic study in comparison with myelodysplastic syndrome-related pseudo-Pelger-Huët anomaly.

Pseudo-Pelger-Huët anomaly (PPHA) has been documented in association with transplant medications and other drugs. This iatrogenic neutrophilic dysplasia is reversible with cessation or adjustment of medications but is frequently confused with myelodysplastic syndrome (MDS) based on the conventional concept that PPHA is a marker for dysplasia. We investigated the clinicopathologic features in iatrogenic PPHA and compared them with MDS-related PPHA. The 13 cases studied included 5 bone marrow/stem cell transplantations, 3 solid organ transplantations, 1 autoimmune disease, 3 chronic lymphocytic leukemias, and 1 breast carcinoma. For 12 cases, there was follow-up evaluation, and all demonstrated at least transient normalization of neutrophilic segmentation. All 9 cases of MDS demonstrated at least 2 of the following pathologic abnormalities on bone marrow biopsy: hypercellularity (8/9), morphologic dysplasia (8/9), clonal cytogenetic abnormality (7/9), and increased blasts (3/9), whereas these abnormalities were typically absent in iatrogenic PPHA. Iatrogenic PPHA displayed a higher proportion of circulating PPHA cells than in MDS (mean, 47.4%; SD, 31.6% vs mean, 12.3%; SD, 9.8; P < .01). A diagnostic algorithm is proposed in which isolated PPHA is indicative of transient or benign PPHA unless proven otherwise.