Foran, James M

Lay Summary People who have advanced myelodysplastic syndromes (MDS) may live longer if they get a bone marrow transplant (BMT) instead of other therapies. However, only 15% of people with MDS actually get BMT. Experts say community physicians and transplant physicians should team up with insurance companies and patient advocacy groups to 1) spread this news about lifesaving advances in BMT, 2) ensure that everyone can afford health care, 3) provide emotional support for patients and families, 4) help patients and families get transportation and housing if they need to travel for transplant, and 5) improve care for people of under‐represented racial and ethnic backgrounds.

BackgroundCXCR4 mediates the retention and survival of acute myelogenous leukemia blasts in bone marrow and contributes to their resistance to chemotherapy. The authors evaluated a combination of the high‐affinity CXCR4 antagonist BL‐8040 with high‐dose cytarabine (HiDAC) chemotherapy in a phase 2a study of patients with relapsed and refractory AML.MethodsForty‐two patients received treatment with BL‐8040 monotherapy for 2 days followed by a combination of BL‐8040 with HiDAC for 5 days. Six escalating BL‐8040 dose levels were investigated (0.5, 0.75, 1.0, 1.25, 1.5, and 2.0 mg/kg), and 1.5 mg/kg was selected as the dose for the expansion phase (n = 23).ResultsBL‐8040 in combination with HiDAC was safe and well tolerated at all dose levels. Clinical response was observed with BL‐8040 doses ≥1.0 mg/kg. The composite response rate (complete remissions plus complete remissions with incomplete hematologic recovery of platelets or neutrophils) was 29% (12 of 42) in all patients and 39% (9 of 23) in the 1.5‐mg/kg phase. The median overall survival was 8.4 months for all patients, 10.8 months in the 1.5‐mg/kg phase, and 21.8 months for responding patients in the 1.5‐mg/kg cohort. Two days of BL‐8040 monotherapy triggered the mobilization of blasts into peripheral blood, with significantly higher mean fold‐changes in responders versus nonresponders. This was accompanied by a decrease in bone marrow blasts.ConclusionsThe current results demonstrate the efficacy of CXCR4 targeting with BL‐8040 and support continued clinical development in acute myelogenous leukemia.

Crystal-storing histiocytosis (CSH) is an uncommon condition in which histiocytes accumulate a crystalline matter within their cytoplasm. Generally, those crystals are composed of either monoclonal or polyclonal immunoglobulin chains, which have a strong association with an underlying lymphoproliferative or plasma cell disorder (LP-PCD). Rarely, CSH has been reported as local or generalized manifestation of a variety of benign disorders. These cases are associated with crystals composed of nonimmunoglobulin substances. We are reporting an exceptional case of a local colonic CSH with Charcot–Leyden crystals. This patient underwent a screening colonoscopy that detected some polyps. The biopsy reported tubular adenomas, with a markedly dense, transmural inflammatory infiltrates, which were predominantly composed of eosinophils and crystal-storing histiocytes containing Charcot–Leyden crystals. The patient had a negative workup for LP-PCD and autoimmune conditions, including a normal skeletal survey and bone marrow aspirate/biopsy. The only positive laboratory workup was an elevated absolute eosinophil count and a positive IgG anti-Strongyloides antibody. Giving those findings, this parasitic infection is the most likely etiology of the CSH in our patient. Although there was an initial negative evaluation for LP-PCD, close monitoring of patients with either immunoglobulin or nonimmunoglobulin CSH is recommended.

Updated WHO criteria define mixed phenotype acute leukemia (MPAL) with more stringent diagnostic criteria than the formerly described entity biphenotypic acute leukemia (BAL). The changes in diagnostic criteria influence management by assigning weight to aberrantly expressed markers and minimizing expression of myeloid markers other than myeloperoxidase (MPO), potentially foregoing consolidative allogeneic transplant for an otherwise “favorable” lymphoid phenotypic leukemia. We present a case of MPO-negative, myeloid antigen-positive acute lymphoblastic leukemia who progressed with refractory phenotypic acute myeloid leukemia while receiving lymphoid-directed therapy and discuss concerns raised by the adoption of the new, more stringent diagnostic criteria for BAL.