The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty-eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (p<0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and >1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (p<0.001). Neurological manifestations, not considered chemotherapy-related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy.
Chronic eosinophilic leukemia-not otherwise specified (CEL-NOS) is a rare disorder with hypereosinophilia and an increased number of blood or marrow blast (<20%) or an evidence of eosinophil clonality. We evaluated the clinical outcome of 10 patients with CEL-NOS. Seven males and three females at a median age of 62 years (range, 23-73) were included. The median leukocyte count at diagnosis was 33.4 3 10 9 /l (range, 9.3-175.0) with a median eosinophil count of 15.6 3 10 9 /l (range, 1.5-136.0). Median hemoglobin and platelets were 11.0 g/dl (range, 8.3-13.3) and 158 3 10 9 /l (range, 31.0-891.0), respectively. Clinical manifestations included splenomegaly (n 5 7), hepatomegaly (n 5 6), cardiac failure (n 5 2), and lung infiltrations (n 5 1). Median survival from diagnosis to death for entire cohort was 22.2 months (range, 2.2-186.2). Five of the 10 studied patients developed acute transformation (AT) after median of 20 months from diagnosis (range, 1.6-41.9). None of patients with AT is alive at the time of last follow-up. Median time from AT to death was 2 months (range, 1.0-6.1). Among five patients who did not develop AT, three died in active disease. Two patients are alive in complete remission; first underwent allogeneic stem-cell transplantation preceding by intensive induction chemotherapy; the second remains on imatinib with hydroxyurea. Except the latter patient, imatinib was ineffective in our study population. CEL-NOS is a rare and aggressive disease with high rate of AT and resistance to conventional treatment.Chronic eosinophilic leukemia-not otherwise specified (CEL-NOS) is a rare Philadelphia-negative myeloproliferative neoplasm, which is due to clonal proliferation of eosinophil precursors. Peripheral blood hypereosinophilia (>1.5 3 10 9 /l), an increased number of myeloblasts in blood or marrow (<20%) or an evidence of eosinophil clonality, are required for diagnosis. The cases of myeloid and lymphoid neoplasms with abnormalities of platelet-derived growth factor alpha (PDGFRA), platelet-derived growth factor beta (PDGFRB), and fibroblast growth factor receptor 1 (FGFR1) must be also excluded [1]. In a new WHO classification, CEL-NOS is listed in the category of myeloproliferative neoplasms [2], whereas it was incorporated under the heading of myeloproliferative forms of hypereosinophilic syndromes according to the classification of the Eosinophilic Working Group [3]. Regardless of the classification used, CEL-NOS remains an extremely rare entity with variable prognosis [1,4]. The efficacy of currently used therapeutic agents is limited, and the hematological responses are usually short-lived [5].Ten patients (seven males and three females) at a median age of 62 years (range, 23-73) were included in this study. The median leukocyte count at diagnosis was 33.4 3 10 9 /l with a median eosinophil count of 15.6 3 10 9 /l. Blood smear was dominated by mature eosinophils with a small number of younger forms, for example, eosinophilic myelocytes and promyelocytes. Single eosinophils had dysplastic fe...
Blood group incompatibility between donor and recipient of allogeneic stem cell transplants may be associated with post-transplant erythroid aplasia. A total of 548 patients (pts) received allogeneic transplant for malignant and non-malignant hematologic disorders. In a retrospective analysis, the prevalence and outcome of pure red-cell aplasia (PRCA) in 44 pts with major and bi-directional ABO-mismatch were investigated. Bone marrow grafts were major ABO incompatible in 30 pts; there was bi-directional mismatch in the remaining 14 pts. The median number of transplanted mononuclear cells (NC) was 4.74 x 10(8)/kg (range 0.1-26.4) including CD34+ cells, 3.02 x 10(6)/kg (range 0.9-21.7). Granulocyte engraftment >0.5 x 10e9/l occurred after a median of 21 days (7-32), and platelet exceeded >50 x 10e9/l after a median of 23.5 days (12-109). Acute and chronic graft vs host disease (GVHD) developed in 23 (52%) and 26 (59%) of the patients, respectively. Six (13%) patients transplanted with major and bi-directional ABO-incompatibility developed PRCA. The treatment of PRCA consisted of plasmapheresis (PEX), rapid cyclosporine (CsA) discontinuation, donor lymphocyte infusions (DLI), erythropoietin (EPO), azathioprine, and rituximab. The therapy resulted in erythroid recovery in five out of six patients after a median of 13 months (range 3-16). The median number of transfused red blood cells (RBCs) was 36 U (range 8-57). With a median follow-up of 37 months, the 5-year probability of overall survival (OS) for the PRCA group was 66%. Major ABO mismatch may lead to delayed donor erythroid engraftment. It results in long-term transfusion dependence and, therefore, the risk of iron overload. The therapy is long lasting, but usually effective in majority of patients.
SummaryHypereosinophilic syndrome (HES) is defined as chronic, unexplained hypereosinophilia with organ involvement. A subset of HES patients presents an interstitial deletion in chromosome 4q12, which leads to the expression of an imatinib‐responsive fusion gene, FIP1L1‐PDGFRA. These patients are diagnosed as chronic eosinophilic leukaemia (CEL). We treated seven CEL and HES patients, six of which expressed FIP1L1‐PDGFRA, with imatinib using initial daily doses ranging from 100 to 400 mg. In a remission maintenance phase, the patients were treated with imatinib once weekly. All imatinib‐treated patients achieved a complete haematological remission (CHR), and five of the six patients with FIP1L1‐PDGFRA expression exhibited molecular remission. The decreased imatinib doses were as follows: 200 mg/week in three patients, 100 mg/week in two patients and 100 mg/d in the remaining two patients. For remission maintenance, imatinib doses were set at 100 mg/week in five patients and 200 mg/week in two patients. At a median follow‐up of 30 months all patients remained in CHR and FIP1L1‐PDGFRA expression was undetectable in five of the six FIP1L1‐PDGFRA‐expressing patients. These data suggest that a single weekly dose of imatinib is sufficient to maintain remission in FIP1L1‐PDGFRA‐ positive CEL patients.
The role of spleen size and splenectomy for the prediction of post‐allogeneic hematopoietic stem cell transplant (allo‐HCT) outcome in myelofibrosis remains under debate. In EBMT registry, we identified a cohort of 1195 myelofibrosis patients transplanted between 2000‐2017 after either fludarabine‐busulfan or fludarabine‐melphalan regimens. Overall, splenectomy was performed in 202 (16.9%) patients and its use decreased over time (28.3% in 2000‐2009 vs 14.1% in 2010‐2017 period). By multivariate analysis, splenectomy was associated with less NRM (HR 0.64, 95% CI 0.44‐0.93, P = .018) but increased risk of relapse (HR 1.43, 95% CI 1.01‐2.02, P = .042), with no significant impact on OS (HR 0.86, 95% CI 0.67‐1.12, P = .274). However, in subset analysis comparing the impact of splenectomy vs specific spleen sizes, for patients with progressive disease, an improved survival was seen in splenectomised subjects compared to those patients with a palpable spleen length ≥ 15 cm (HR 0.44, 95% CI 0.28‐0.69, P < .001), caused by a significant reduction in NRM (HR 0.26, 95% CI 0.14‐0.49, P < .001), without significantly increased relapse risk (HR 1.47, 95% CI 0.87‐2.49, P = .147). Overall, despite the possible biases typical of retrospective cohorts, this study highlights the potential detrimental effect of massive splenomegaly in transplant outcome and supports the role of splenectomy for myelofibrosis patients with progressive disease and large splenomegaly.
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