Suspected Immune Thrombocytopenic Purpura Induced by Lenalidomide for the Treatment of Myelodysplastic Syndrome with Deletion of Chromosome 5q: A Case Report.

Lenalidomide (LEN), one of the key drugs in the treatment of myelodysplastic syndromes (MDS) with 5q deletion, as well as multiple myeloma (MM), has various immunomodulatory effects and has been associated with autoimmune diseases, including immune thrombocytopenic purpura (ITP). A 78-year-old man presented with pancytopenia and was diagnosed with MDS with 5q deletion and other chromosomal abnormalities. Two cycles of LEN therapy (one cycle: 10 mg/day for 21 days) resulted in a transient improvement in anemia, followed by MDS progression with severe thrombocytopenia (4 × 109/L) refractory to platelet transfusions. As other non-immune and alloimmune causes of transfusion-refractory thrombocytopenia were excluded, and the level of platelet-associated immunoglobulin G was extremely high compared with the level before treatment with LEN, the diagnosis of ITP was highly suspected. Despite treatment with prednisolone (PSL), eltrombopag, and repeated platelet transfusions, his platelet count did not increase, and he died of a gastrointestinal hemorrhage. Several cases of ITP induced by LEN used to treat MM had been reported, but the platelet count recovered after administration of PSL in these previous cases. However, we should be mindful of using LEN for patients with MDS because its treatment may become extremely difficult if ITP develops.

Spontaneous Regression of Blastic Plasmacytoid Dendritic Cell Neoplasm Following Sepsis by Serratia marcescens: A Case Report and Literature Review.

Spontaneous regression is rare in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). An 85-year-old man presented with pancytopenia and skin lesions, and the bone marrow exhibited 79.6% CD4+, CD56+, CD123+, and TCL-1+ abnormal cells, with a normal karyotype; he was thus diagnosed with BPDCN. While being followed without chemotherapy, he was admitted due to sepsis induced by Serratia marcescens, which was successfully treated with antibiotics. Notably, his blood cell counts improved, and the skin lesions disappeared. To our knowledge, this is the first reported case of spontaneous regression of BPDCN with a decrease in tumor cells in the bone marrow following sepsis.

A case study of t(14;22)(q32;q11) involving immunoglobulin heavy and light chain in follicular lymphoma.

Chromosome 14 is the most frequently rearranged chromosome in non-Hodgkin lymphoma (NHL), with aberrations particularly involving the heavy-chain immunoglobulin gene (IGH) in the chromosome band 14q32. Several translocation partners have been described: t(14;18)(q32;21)/IGH-BCL2 in follicular lymphoma (FL), t(11;14)(q13;q32)/CCND1-IGH in mantle cell lymphoma, and t(8;14)(q24;q32)/MYC-IGH in Burkitt lymphoma. The chromosomal locus 22q11 contains two important genes associated with leukemia and lymphoma; one is BCR, which fuses with ABL from 9q34 in chronic myeloid leukemia, and the other is the immunoglobulin lambda gene (IGL), which is rarely involved in the translocations observed in B-cell NHL. The t(14;22)(q32;q11) translocation has been previously reported in 8 cases of B-cell NHL; however, the translocation between IGH and IGL has been experimentally confirmed using fluorescence in situ hybridization (FISH) for only 4 cases. Here, we describe the first case of FL with a t(14;22)(q32;q11)/IGH-IGL translocation confirmed using FISH analysis. The patient in our case report was immunocompromised and was treated for aplastic anemia with cyclosporine A (CsA). The patient was diagnosed with follicular lymphoma, most likely caused by CsA.

A new complex translocation t(5;17;15)(q11;q21;q22) in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is associated with the t(15;17)(q22;q21) translocation which causes the fusion of the retinoic acid alpha gene (RARA) on 17q21 to the promyelocytic leukemia gene (PML) on 15q22. The two chimeric genes, PML/RARA and RARA/PML, are thought to play a role in leukemogenesis. A small proportion of patients with APL have complex or simple variants of this translocation. We report the case of a 22-year-old woman with APL carrying a complex variant translocation t(5;17;15)(q11;q12;q22) confirmed by G-banding, reverse transcription polymerase chain reaction (RT-PCR), fluorescence in situ hybridization(FISH), and spectral karyotyping analysis (SKY). The patient achieved complete remission with all-trans retinoic acid treatment and chemotherapy. These results illustrate the usefulness of combined analysis consisting of G-banding, RT-PCR, FISH, and SKY methods to identify the PML/RARA fusion gene in cases with variant t(15;17).

Increased expression of insulin-like growth factor i is associated with Ara-C resistance in leukemia.

Resistance to cytosine arabinoside (Ara-C) is a major problem in the treatment of patients with acute myeloid leukemia (AML). In order to investigate the mechanisms involved in Ara-C resistance, the gene expression profile of Ara-C-resistant K562 human myeloid leukemia cells (K562/AC cells) was compared to that of Ara-C-sensitive K562 cells (K562 cells) by using a cDNA microarray platform. Correspondence analysis demonstrated that insulin-like growth factor I (IGF-I) gene was upregulated in K562/AC cells. The biological significance of IGF-I overexpression was further examined in vitro. When K562 cells were incubated with IGF-I ligand, they were protected from apoptosis induced by Ara-C. In contrast, a significant inhibition of growth and increase of apoptosis of K562/AC cells were induced by IGF-I receptor neutralizing antibody, or suramin, a nonspecific growth factor antagonist. Moreover, from the analysis of 27 AML patients, we have shown that IGF-I expression levels are higher in patients at refractory stage, after Ara-C combined chemotherapy, than those in patients at diagnosis. These results suggest that the inhibition of IGF-I and its downstream pathway is a valuable therapeutic approach to overcome Ara-C resistance in AML.

Detection of clone-specific immunoglobulin heavy chain genes in the bone marrow of B-cell-lineage lymphoma after treatment.

In order to determine the appropriate treatment of malignant lymphoma, it is important to know the degree to which extra-nodal invasion of lymphoma cells has occurred. We amplified complementarity-determining region (CDR) III genes in 64% of lymph node samples at the onset or relapse of B-cell-lineage non-Hodgkin's lymphoma (NHL) in 22 patients. By using a clone-specific CDR III probe in each patient, we were able to detect minimal residual disease (MRD) of lymphoma cells in the bone marrow and/or blood in 9 out of 14 cases (64.2%) at the onset of the disease or relapse, whereas abnormal cells in the bone marrow and/or blood were identified by routine morphological analysis in only 4 out of 22 cases (18.2%). This indicates that extranodal invasion of malignant cells may be common in patients with NHL. In some cases, the clone-specific CDR III gene was still expressed in the samples of bone marrow and/or peripheral blood even after chemotherapy, when other markers associated with NHL were no longer expressed. Five out of six cases in this group had a worse outcome associated with NHL. On the other hand, most of the cases whose clone-specific CDR III gene was no longer expressed in the bone marrow and/or in circulation after treatment had a relatively fair prognosis. These results indicate that the detection at molecular level of MRD in extranodal organs may prove useful as a predictor of prognosis for NHL.