Lenalidomide therapy in myelofibrosis with myeloid metaplasia.

We present results of 2 similarly designed but separate phase 2 studies involving single-agent lenalidomide (CC-5013, Revlimid) in a total of 68 patients with symptomatic myelofibrosis with myeloid metaplasia (MMM). Protocol treatment consisted of oral lenalidomide at 10 mg/d (5 mg/d if baseline platelet count < 100 x 10(9)/L) for 3 to 4 months with a plan to continue treatment for either 3 or 24 additional months, in case of response. Overall response rates were 22% for anemia, 33% for splenomegaly, and 50% for thrombocytopenia. Response in anemia was deemed impressive in 8 patients whose hemoglobin level normalized from a baseline of either transfusion dependency or hemoglobin level lower than 100 g/L. Additional treatment effects in these patients included resolution of leukoerythroblastosis (4 patients), a decrease in medullary fibrosis and angiogenesis (2 patients), and del(5)(q13q33) cytogenetic remission accompanied by a reduction in JAK2(V617F) mutation burden (1 patient). Grade 3 or 4 adverse events included neutropenia (31%) and thrombocytopenia (19%). We conclude that lenalidomide engenders an intriguing treatment activity in a subset of patients with MMM that includes an unprecedented effect on peripheral blood and bone marrow abnormalities.

Clinical spectrum of myelophthisis in cancer patients.

Myelophthisis is a form of bone marrow failure due to replacement of hematopoietic tissue by abnormal tissue, most commonly metastatic carcinomas. This results in extramedullary hematopoiesis, typically in the spleen leading to premature release of hematopoietic cells into the circulation. Peripheral blood findings may include nucleated red blood cells, tear drop forms, giant platelets, and immature leukocytes. This is called a leukoerythroblastic picture. The first case demonstrates acute myelophthisis as a presentation of pancreatic cancer. The second case is of extramedullary hematopoiesis as a manifestation of widely metastatic melanoma. The presence of a leukoerythroblastic peripheral blood picture should serve as a valuable clue about a possible underlying malignancy. This late presentation of advanced cancer may now be rarely seen because of early diagnosis and more effective therapies.

Leukoerythroblastic anemia in metastatic prostate cancer. Clinical and prognostic significance in patients with hormone-refractory disease.

BACKGROUND: The clinical and prognostic significance of leukoerythroblastic anemia (LKEA) in patients with metastatic prostate cancer and, in general, patients with disseminated solid tumors is poorly understood. Therefore, the authors studied a population of patients with metastatic prostate cancer refractory to hormonal therapy to assess the incidence, clinical features, and prognostic implications of LKEA. METHODS: The medical records of 106 patients with hormone-refractory prostate cancer metastatic to bone seen at the Tucson Veterans Affairs Medical Center between 1985 and 1991 were reviewed retrospectively. The clinical and laboratory data, number of packed erythrocyte transfusions required, and length of survival from the time of diagnosis of hormone-refractory disease until last follow-up visit or death were investigated in 91 identified patients. RESULTS: Twenty-six of 91 patients (28.6%) were found to have LKEA. LKEA developed before or at the time of diagnosis of hormone-refractory disease in 8 patients and after diagnosis of hormone-refractory disease in 18 patients. The presence of LKEA was associated with significantly lower hemoglobin levels and platelet (Plt) counts and significantly higher total bilirubin, lactic dehydrogenase (LDH), and alkaline phosphatase values (P < 0.05). Leukopenia (< 4.0 x 10(9)/l leukocytes), thrombocytopenia (< 150 x 10(9)/l Plt), elevated LDH levels (> 220 U/l), and laboratory evidence of disseminated intravascular coagulation (DIC) were more common in patients with LKEA than in those without LKEA (P < 0.01). Microangiopathic hemolysis was seen in only 2 of 91 patients (2.1%). Patients with LKEA had significantly greater transfusion requirements compared with patients without LKEA (P < 0.0001), but the median survival length was not significantly different (9 months versus 11 months, respectively). The presence of DIC and LDH levels of 500 U/l or greater in patients with LKEA was associated with a poor prognosis. CONCLUSIONS: LKEA is a relatively common finding in patients with hormone-refractory metastatic prostate cancer and is associated with greater transfusion requirements. Its presence, however, does not affect survival significantly.

Clinical significance of hematologic parameters in non-Hodgkin's lymphoma at diagnosis.

Three hundred seventeen patients with non-Hodgkin's lymphoma (NHL) (54 low grade, 180 intermediate grade, 76 high grade, and seven unclassified) treated with chemotherapy were evaluated for the presence of hematologic abnormalities at diagnostic staging. Anemia was present in 42%, leukopenia in 6%, thrombocytopenia in 13%, leukocytosis in 26%, and thrombocytosis in 14% at presentation. The presence of bone marrow involvement by lymphoma was more likely to be associated with leukopenia and thrombocytopenia than the absence of bone marrow involvement. Although anemia was slightly more common in patients with bone marrow lymphoma than in those without marrow lymphoma, the difference was not statistically significant. Hematologic parameters were similar for patients with B-cell or T-cell lymphoma. Evidence of bone marrow failure with multiple cytopenias was present in 26 patients (8%). Leukoerythroblastosis was present in 2%. Circulating lymphoma was present in 9.5%. Anemic patients had a shorter survival time than nonanemic patients, whether bone marrow was involved by lymphoma or not. Survival was not affected by the presence of leukopenia or mild leukocytosis, but, in patients without marrow lymphoma, leukocytosis with a leukocyte count greater than 20 x 10(9)/l was associated with short survival length. Thrombocytopenia was associated with short survival time only in patients with bone marrow involvement by lymphoma. Patients with multiple cytopenias or leukoerythroblastosis had short survival times, but the presence of circulating lymphoma did not alter survival when compared with other patients with bone marrow involvement by lymphoma. These data suggest that hematologic evaluation at the time of diagnostic staging of NHL provides useful prognostic information that may have therapeutic implications.

[Megakaryocyte proportion versus nucleated cells in the peripheral blood showing leukoerythroblastosis].

Megakaryocytes in the peripheral blood in which leukoerythroblastosis was recognized were studied by electron microscopy on the vertically cut section of the buffy coat of the blood, and percentages of them in 10,000 nucleated cells distributed from the top of the bottom of the buffy coat were counted. In 15 of 31 patients, percentages of peripheral blood megakaryocytes ranging from 0.01% to 0.64% were seen. There was difference of the result among diseases shown peripheral blood megakaryocytes. Namely, in patients with myelofibrosis and CML, in whom extramedullary hematopoiesis was predominant, many cases ascertained peripheral blood megakaryocytes were demonstrated. Because of this result, the extramedullary hematopoiesis appears to play an important role to the presentation of megakaryocytes in the peripheral blood. On the other hand, patients indicating both megakaryocytes and abnormal sideroblasts in the peripheral blood had sideroblastic anemia marrow. This result seems to show that a part of megakaryocytes are directly flowed out from the marrow into the blood simultaneously accompanied with abnormal sideroblasts.

Biochemical values, complement levels, and hemostatic data in septic leukoerythroblastosis.

Recently, the association of granulocytic fragments on blood smear with leukoerythroblastosis in sepsis has been identified in nine patients. Granulocytic fragments were identified by both light and electron microscopy as well as cytochemistry. Leukoerythroblastosis is a poorly defined, uncommon syndrome with leukocytosis, left shift, and nucleated red blood cells (nRBCs) disproportionate to the degree of anemia, which may be associated with leukemia or neoplasia in the bone marrow, acute infection, hemolysis, myelofibrosis, or miscellaneous causes. Here a subgroup with high white blood cells (WBC) and acute infection was studied. The corrected WBC for nine patients was 40 x 10(9) per L with 33 nRBC per 100 WBC; serum C3 and C4 levels before and after the development of leukoerythroblastosis were 0.6 +/- 2 g per L; 0.18 +/- 0.04 g per L pre-leukoerythroblastosis and 0.7 +/- 0.46 g per L; 0.30 +/- 0.27 g per L post-leukoerythroblastosis, respectively, in four patients. The platelet count, prothrombin time (PT), and activated partial prothrombin time (aPTT) were 133 x 10(9) per L, 24.4 sec., and 53.5 sec., respectively, for nine patients. Multiphasic chemistries at the time of leukoerythroblastosis were measured in five patients; abnormal values included calcium of 2.0 +/- 0.4 mmol per L, creatinine of 336 +/- 130 mumol per L, total protein of 45 +/- 17 g per L, albumin of 27 +/- 11 g per L, total bilirubin of 421 +/- 362 mumol per L, uric acid of 499 +/- 264 mumol per L, triglycerides of 4.9 +/- 3.7 mmol per L, and alkaline phosphatase of 3.5 +/- 1.0 mu kat per L.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone marrow involvement in small cell lung cancer. Clinical significance and correlation with routine laboratory variables.

Of 129 patients with small cell lung cancer (SCLC) who underwent bone marrow examination for staging, 39 (30%) had bone marrow involvement. Only three of 129 patients (2.3%) had bone marrow involvement as the only site of metastatic disease. When patients with bone marrow metastasis were compared with patients whose bone marrow was normal, there were significant differences in serum levels of lactate dehydrogenase (LDH), glutamic oxalacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT), alkaline phosphatase (AP), albumin, and sodium (Na). We found no clinically significant difference in survival between patients with extensive disease with or without bone marrow involvement. Serum Na, albumin, SGOT, and uric acid were important prognostic determinants of survival. Based on the results of this study, we do not recommend routine bone marrow examinations in the staging of SCLC.

Normoblasts in peripheral blood of Nigerians: their clinical significance.

The clinical conditions associated with peripheral blood nucleated red blood cells (NRBC) in Nigerians were investigated prospectively to define them and establish their mortality. Of the 4,565 differential counts carried out within ten months, NRBC were detected in 120 cases (2.6 percent). Of these, severe nutritional anemia was seen in 64.4 percent, sickle cell anemia in 23.8 percent, neonatal status in 7.6 percent; and malignant diseases in 4.2 percent. Leukoerythroblastosis occurred in 11 percent. The overall mortality was 4.2 percent, and among those with congestive cardiac failure, there was no fatality. These results show that malignancy is not a major cause of normoblasts in peripheral blood in this environment and that the prognosis is not as poor as has been reported in some North American and European literature.

[Leukoerythroblastosis as a manifestation of disseminated neuroblastoma in childhood]. / La leucoeritroblastosis como manifestación de neuroblastoma diseminado en la infancia.

A check is made of the hematologic disorders in 20 children with neuroblastoma and its relation with the stage of the tumour. The 75% of the patients had metastasis when they are examined, 70% anemia, 15% leukopenia, 20% thrombopenia and 50% leukoerythroblastosis. The patients with leukoerythroblastosis all had remote metastasis and made up 66% of the children with IV or IV-S stage. In 50% of the patients there was metastasis in the bone marrow and 80% of these had leukoerythroblastosis.

Acute myelomonocytic leukemia manifested as myelophthisic anemia in a dog.

A 10-year-old, Golden Retriever-type castrated male dog was found to have a hemogram consistent with myelophthisic anemia. Within 30 days the hemogram changed in such a manner that a myeloproliferative disorder was evident. On the basis of hematologic, cytochemical, and cytologic findings, acute myelomonocytic leukemia was diagnosed.

Leucoerythroblastic anaemia in carcinoma of ovary.

The survey of cases of ovarian carcinoma referred to the Radiotherapy Centre at Sheffield between 1956 and 1965 was undertaken, which revealed one case of leucoerythroblastic anaemia as a complication. This patient also had a demonstrable bony metastases, which appeared eight years after the apparent cure of the diasease-a most unusual feature of carcinoma of ovary.