Reduced-intensity conditioning allogeneic transplantation after salvage treatment with DT-PACE in myeloma patients relapsing early after autologous transplant.

OBJECTIVE: In this retrospective single-centre study, we have looked into the transplant outcomes(overall survival OS, progression-free survival PFS, GvHD) and the role of chimerism, DLI and pretransplant characteristics in patients who had a suboptimal response (<12 months) to an autologous stem cell transplant for myeloma and underwent an alemtuzumab T-cell depleted reduced-intensity allograft(RIC). METHODS: Twenty-four patients were salvaged with two cycles of DT-PACE and received a RIC transplant with fludarabine, melphalan and alemtuzumab. All the patients received PBSC grafts, eight patients had a sibling donor, and 16 had a graft from a fully matched unrelated donor. The median follow-up was 65.3 months (6-132 months). RESULTS: The median overall survival was 55.4 months. DLI administration was associated with a trend towards better overall survival (P=.05). Disease status at allo-HCT, PR or VGPR, ISS score and CMV serostatus was not significant predictors of OS and PFS. Full donor whole blood chimerism (≥98%) at 3 months post-transplant was associated with PFS (P=.04) but did not have a significant impact on OS(P=.45). CONCLUSION: Reduced-intensity alemtuzumab-conditioned allograft for myeloma after DT-PACE salvage chemotherapy is an efficient and low toxicity treatment for those who had a suboptimal response postautologous stem cell transplant for myeloma.

Multiple cutaneous reticulohistiocytosis with T-cell large granular lymphocyte clonopathy.

A 63-year-old Caucasian man presented with a 4-month history of disseminated asymptomatic reddish-brown papulonodular lesions. A skin biopsy showed dermal infiltration with CD68+ histiocytes, predominantly with eosinophilic cytoplasm, some with a ground-glass cytoplasm, and a small number of giant cells. The diagnosis of multiple cutaneous reticulohistiocytosis was made. Bone marrow immunophenotyping due to peripheral blood lymphocytosis revealed the presence of a monoclonal population of CD3+ , CD8+ CD57+ large granular lymphocytes. The present case suggests the coexistence of multiple cutaneous reticulohistiocytosis with an underlying disorder.

The relationship between soluble receptor of interleukin-6 with angiogenic cytokines and proliferation markers in multiple myeloma.

Soluble interleukin-6 receptor (sIL-6R) is part of IL-6 receptor that may stimulate cells that do not express the whole molecule. It may enhance myeloma cell proliferation and furthermore angiogenesis. The aim of the study was to evaluate the clinical significance and the relationship between serum levels of sIL-6R, with various stimulators of angiogenesis, such as hepatocyte growth factor (HGF) and interleukin-18 (IL-18) and with markers of proliferation, such as beta-2 microglobulin (B2M) levels and plasma cell Ki-67 proliferation index in the bone marrow, in patients with multiple myeloma (MM). We studied 45 newly diagnosed MM patients. Serum levels of sIL-6R, HGF, IL-18, and B2M and Ki-67 proliferation index (Ki-67 PI) in bone marrow's plasma cells were determined. The mean concentrations of sIL-6R, HGF, IL-18, and B2M and the value of Ki-67 were significantly higher in the patients compared to controls and with increasing disease stage. sIL-6R was strongly positively correlated with HGF, IL-18, B2M, and Ki-67 PI. There is a positive correlation between plasma cell growth, as determined by Ki-67 PI, and different angiogenic cytokines, such as HGF and IL-18, with sIL-6R. This relationship suggests the significant role of these cytokines in the proliferation and disease activity in MM patients.

Enhanced levels of the apoptotic BAX/BCL-2 ratio in children with acute lymphoblastic leukemia and high-risk features.

It has been suggested that leukemia is characterized by an impaired balance between the proliferation of blood cells and their capacity to undergo apoptosis. The aim of this study was to examine the expression of key molecules related to apoptosis (BCL-2, BAX, FAS, FAS-L) in children with acute lymphoblastic leukemia (ALL). Measurement of BCL-2 and BAX mRNA was performed by quantitative real-time PCR, and membrane expression of FAS and FAS-L was assessed by flow cytometry in bone marrow mononuclear cells, both at diagnosis and at remission following induction chemotherapy. At diagnosis, increased levels of the apoptotic BAX/BCL-2 ratio were observed in children older than 10 years and with higher white blood cell counts. A DNA index < 1.16 was associated with increased BAX/BCL-2, both at diagnosis and at remission, and the del(9p) chromosome abnormality with increased BAX/BCL-2 at remission. The expression of the apoptotic receptor FAS was significantly higher at remission compared to diagnosis, which might reflect enhanced sensitivity of the leukemic clone to apoptosis and response to treatment. Altogether, our results highlight the association of apoptosis-related genes with clinical and cytogenetic prognostic parameters in pediatric ALL. A better understanding of the mechanisms and regulation of apoptosis should enable the design of novel targeted therapies for these patients.

Nodular Lymphocyte Predominant Hodgkin Lymphoma With Aberrant Immunophenotype or Variant Histopathology: Insights From Case Series of Three Patients.

BACKGROUND: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) with variant histopathology or aberrant immunophenotype is exceedingly rare and there is paucity of data with regards to its clinical characteristics and course. CASE REPORT: Herein, we present three cases of NLPHL with aberrant immunophenotype or variant histopathological picture, which displayed distinct clinical and imaging findings. These case reports involved a patient with CD30 and CD20 positivity without Reed-Sternberg cells present, a NLPHL patient with aggressive, persistent disease activity with progressive transformation to germinal centres, and a patient with combined morphology of NLPHL and classical Hodgkin's lymphoma. CONCLUSION: Aberrant immunophenotype/variant NLPHL might represent a distinct form of NLPHL, sharing characteristics with classical Hodgkin, non-Hodgkin lymphomas or benign, progressive transformation of germinal centre lymphadenopathy.

Management of Allogeneic Stem Cell Transplantation for High-Risk AML following SARS-CoV-2 Associated Pancytopenia with Marked Bone Marrow Biopsy Alterations.

The present study describes a patient aged 70 with very high-risk AML who successfully received a nonmyeloablative matched unrelated donor allograft shortly following SARS-CoV-2 infection, which manifested with mild cough, interstitial abnormalities on chest CT, and pancytopenia with profound bone marrow biopsy histological alterations. In parallel, our study provides bone marrow biopsy data in a series of contemporary patients with serious haematological diseases who had a bone marrow biopsy performed within two weeks of PCR confirmation of SARS-CoV-2 infection. This study is notable because there are no published data describing the bone marrow biopsy changes observed in patients with haematological malignancies and SARS-CoV-2 infection. Finally, it is suggested that nonmyeloablative hematopoietic stem cell transplantation for very high-risk haematological malignancies can be successfully performed following recovery from SARS-CoV-2 infection.

Autoimmune Cytopenias Developing Late Post Alemtuzumab-Based Allogeneic Stem Cell Transplantation: Presentation of Short Case Series from a Transplant Center.

Stem cell transplantation remains the curative option for many patients with hematological malignancies. The long-term effects of these treatments on the patients and their immune systems have been extensively investigated, but there remains a paucity of data regarding autoimmune manifestations post-transplant, although these effects are well recognized.Herein we present the clinical picture and therapeutic approach in three patients (cases 1-3), with varied presentations of autoimmune disease post-transplant. Case 1 exhibited autoimmune hemolytic anemia and other autoimmune manifestations (serositis, thyroiditis), that were probably linked to graft versus relapsed leukemia effect. Cases 2 and 3 had pure red white cell aplasia and pure red cell aplasia, respectively, which were associated with hyperglobulinemia and a clonal T cell expansion.

First case of near haploid philadelphia negative B-Cell acute lymphoblastic leukaemia relapsing as acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation.

Herein we present a female patient aged 61 with Philadelphia negative acute lymphoblastic leukaemia demonstrating near haploid karyotype and abnormal TP53 expression at diagnosis, who relapsed with lineage switch as Acute Monocytic Leukemia post allogeneic stem cell transplantation. Molecular analysis established that both neoplasms were derived from the same founder clone. The leukemic lineage switch phenomenon has recently re-attracted interest as mechanism of leukemic evasion post treatment with chimeric antigen receptor T-cells but there is paucity of data on its presence post allograft or following novel antibody treatments such as Inotuzumab Ozogamicin or Blinatumomab. Our proposition for cancer research is that near haploidy in ALL could be linked to leukemic stem cell plasticity evading stem cell transplantation and other immunotherapy approaches.

Coexistence of plasma cell dyscrasia with prefibrotic stage of primary myelofibrosis: a case report.

Introduction. Coexistence of myeloproliferative neoplasms with lymphoproliferative syndromes has been described in the past, whereas plasma cell dyscrasias seem to be the most common cases. Case Presentation. We present a case of a 59-year-old Caucasian female of Greek origin who presented with thrombocytosis. Clinical and laboratory investigation disclosed the presence of a smoldering myeloma with coexisting histological and molecular characteristics of primary myelofibrosis. The patient had the acquired point mutation V617F in the JAK2 gene but not the bcr-abl rearrangement and was treated for myelofibrosis with subsequent improvement of all haematological parameters without evidence of myelomatic evolution. Conclusion. We present the first case in the literature of a smoldering myeloma coexisting with primary myelofibrosis. The underlying pathogenetic mechanism could be either related to the presence of a pluripotent neoplastic stem cell capable to differentiate into both lymphoid and myeloid cells or be related to two separate nosologic entities.