Hematology

Correction to: Numerous Russell bodies in multiple myeloma Owing to an unfortunate mistake at the typesetter’s end, Figure 1 was published incorrectly which is corrected in this correction.

Correction to: Thalidomide maintenance therapy in Japanese myeloma patients: a multicenter, phase II clinical trial (COMET study) The authors would like to correct the errors in the publication of the original article. The correction details are given below.

Primary ALK-negative anaplastic large cell lymphoma with extensive bone involvement mimicking multiple myeloma and metastatic carcinoma

Guest Editorial: Are “alternative” stem cell sources still alternative in the new era?

Successful hematopoietic stem-cell mobilization with plerixafor plus granulocyte-colony stimulating factor in multiple myeloma patients treated with pomalidomide Abstract Autologous stem-cell transplantation is an effective procedure for the treatment of multiple myeloma, and involves the collection of hematopoietic stem cells (HSCs). However, in some patients, HSCs in the bone marrow fail to mobilize. Pomalidomide upregulates CXCR4 in hematopoietic stem cells, in a manner similar to that of lenalidomide, and is, thus, likely to have a negative impact on hematopoietic stem-cell mobilization in multiple myeloma patients. Here, we report the two cases in which hematopoietic stem cells were mobilized using plerixafor plus granulocyte-colony stimulating factor after exposure to lenalidomide and pomalidomide. Use of plerixafor with a sufficient washout period may lead to successful mobilization following pomalidomide use, although further study of this potential use is needed.

Expression analysis of two SLAM family receptors, SLAMF2 and SLAMF7, in patients with multiple myeloma Abstract Monoclonal antibodies against surface antigens on MM cells, such as anti-SLAMF7 and anti-CD38 antibodies, represent an attractive therapeutic modality for the eradication of multiple myeloma (MM) cells. However, further exploration of target molecules is urgently needed for the development of more effective therapies. In the present study, we studied the expression of CD48 in a total of 74 primary MM samples derived from patients to evaluate SLAMF2 (CD48) as a candidate in mAb therapy for MM. Of 74 samples, 39 were subjected to SLAMF7 analysis. Most of the MM cells, defined as CD38 and CD138 double-positive cells, showed strong expression of CD48 or SLAMF7 independent of disease stage or treatment history. In these 39 samples, most MM cells showed expression of both SLAMF7 and CD48; however, several samples showed expression of either only CD48 or only SLAMF7, including seven cases that were only highly positive for SLAMF7, and five that were only highly positive for CD48. Our study demonstrates that the immune receptor CD48 is overexpressed on MM cells together with SLAMF7, and that CD48 may be considered as an alternative target for treatment of MM in cases showing weak expression of SLAMF7.

HLA-haploidentical stem cell transplantation using posttransplant cyclophosphamide Abstract HLA-haploidentical stem cell transplantation using posttransplant cyclophosphamide has spread rapidly worldwide. This strategy was initially developed in the setting of bone marrow transplantation following nonmyeloablative conditioning. Recently, peripheral blood stem cell grafts and/or myeloablative conditioning regimen have been widely used. In Japan, prospective, multicenter, phase II studies have been conducted by the Japan Study Group for Cell Therapy and Transplantation to evaluate the safety and efficacy of HLA-haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide (PTCy-haploPBSCT). In the first such study (JSCT Haplo 13 study), we demonstrated that PTCy-haploPBSCT after busulfan-based reduced-intensity conditioning (RIC) enables stable donor engraftment and low incidences of both acute and chronic graft-versus-host disease (GVHD). In the second (JSCT Haplo 14 study), we showed that both myeloablative conditioning (MAC) and RIC are valid options for PTCy-haploPBSCT. Emerging evidence, including our findings, suggests that donor type (HLA-haploidentical donor versus HLA-matched related or unrelated donor) may no longer be a significant predictor of transplant outcome.

Effect of antithymocyte globulin on HLA-mismatched unrelated transplantation Abstract HLA 1-locus-mismatched unrelated donors (1MMUD) are often considered as alternative donors in allogeneic hematopoietic stem-cell transplantation (allo-HCT) when an HLA-matched related or unrelated donor is unavailable. However, HLA mismatch remains a major risk factor for acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) has been used to prevent acute and chronic GVHD, and multiple studies have shown that use of ATG is associated with decreased acute and chronic GVHD, which is associated with improved QOL. However, at high doses, ATG may lead to an increase in fatal infection, relapse, or delayed engraftment. The optimal ATG dose for MMUD remains unclear. The optimal ATG dose should be determined based on a fine balance between the reduction of GVHD and the risk of relapse, fatal infection, and/or delayed engraftment. Interestingly, promising results from some recent Asian studies suggest that a low dose of ATG may improve non-relapse mortality and overall survival without increasing relapse or fatal infection in allo-HCT from an HLA-mismatched unrelated donor. A randomized control trial is expected to confirm these results in Japan. In addition, pharmacokinetic/pharmacodynamic studies may help to identify the personalized optimal ATG dose.

Current and future perspectives on allogeneic transplantation using ex vivo expansion or manipulation of umbilical cord blood cells Abstract In patients with hematologic malignancies, the outcome of umbilical cord blood transplantation has improved and is now comparable to that of matched unrelated donor transplantation. However, the limitation of using umbilical cord blood has been a delay in both hematopoietic and immunologic recovery. Strategies have been proposed to overcome these limitations. One strategy involves ex vivo expansion of the umbilical cord blood unit prior to transplantation. A second strategy involves exposure of the umbilical cord blood graft to compounds aimed at improving homing and engraftment following transplantation. Many of these strategies are now being tested in late phase multi-center clinical trials. If proven cost effective and efficacious, they may alter the landscape of donor options for allogeneic stem cell transplantation.

Germline missense NF1 mutation in an elderly patient with a blastic plasmacytoid dendritic cell neoplasm Abstract Neurofibromatosis type 1 is an autosomal dominantly inherited tumor predisposition syndrome, in which inactivating mutations in the neurofibromatosis type 1 gene (NF1) lead to a prolonged activation of the signaling via the RAS/RAF/MAPK pathway leading to loss of growth control and increased cellular proliferation. We report a case of a 78-year-old man, a carrier of the germline NF1 Ala1224Gly/c.3671 C>G mutation, with ASXL1, ZRSR2 and TET2 mutation-positive blastic plasmacytoid dendritic cell neoplasm (BPDCN). Consistent with previously reported data on the role of the NF1 mutations in the pathogenesis of dendritic cell neoplasms, we suggest that the NF1 germline mutation may also increase the risk of BPDCN.