Meningeal leukemia in the blastic phase of chronic granulocytic leukemia

One hundred one patients were treated for Ph' positive chronic granulocytic leukemia (CGL) In the blastlc phase. In seven of these (6.9 per cent), meningeal leukemia developed. Of the 99 patients who died of their disease, a complete remission was achieved In 12 with a median survival of 12 months (three to 28 months). Incomplete responders had a median survival of only 2.5 months (one to 14 months). In five of the 12 complete responders (42 per cent), but in only two of the incomplete responders (2.3 per cent), meningeal leukemia developed. The principal neurologic signs were cranial nerve palsies and papilledema. AH patients had pleocytosis with myetoblasts in the cerebrosplnal fluid. As in patients with acute leukemia and diffuse histiocytic lymphoma, increased survival of patients in whom hematologic remission from the blastlc phase of CGL is achieved may allow sufficient time for the development of meningeal leukemia. Intrathecal methotrexate is extremely successful in treating this complication. Cerebrospinal fluid pleocytosis was eradicated in all seven of our patients, and neurologic symptoms and signs were completely eliminated in five patients. No evidence of meningeal leukemia was found in three of the five patients in whom an autopsy was performed.     

Pericarditis revealing chronic myelomonocytic leukemia

We report the case of a 67-year-old man who developed pericarditis as the initial manifestation of myelomonocytic leukemia. Leukemic pneumonitis developed 4 months later and the patient later died.     

Alpha interferon in the treatment of chronic myelomonocytic leukemia

This study aimed at evaluating the effectiveness of alpha interferon (IFN) in chronic myelomonocytic leukemia, a disease for which therapeutic options are still unsatisfactory. Fourteen sequential unselected patients received recombinant alpha-2b IFN (Intron-A, Schering-Essex) 3 megaU/day, progressively elevated to 10 megaU/day in non responders. Rate and type of response were evaluated in the 10 patients who completed a minimum treatment period of three months. Monocytosis, present in all patients by definition, was reduced in 8 of these 10; neutrophils decreased in 5 of 7 patients with high initial values. Signs of ineffective hemopoiesis were generally not influenced by the treatment, nor were organomegaly and hypergammaglobulinemia, when present; however, in 4 patients the Hb level improved with treatment. IFN treatment failed to improve in vitro growth of GM colonies, but there was improvement of the cluster/colony ratio, due to decrease number of clusters. Lysozyme production by pathologic monocytes was inhibited in the presence of IFN in vitro. Tolerance was variable: three patients interrupted the treatment for unmanageable side effects. These results show that alpha IFN can be effective in CMML patients with prominent proliferative aspects.     

Low-dose etoposide in the treatment of chronic myelomonocytic leukemia

Two cases of chronic myelomonocytic leukemia (CMML) which were successfully treated with low dose etoposide are reported. One case was treated with oral etoposide in daily dose of 25 mg for 3d a week, another case in dose of 50 mg/day. Their white blood cell counts became normal and monocytes decreased after the treatment with etoposide. In the second case, blasts in peripheral blood disappeared and thrombocytopenia was improved. The experience of these cases suggests that low dose etoposide is an useful treatment for CMML.     

Granulocytic sarcoma of the colon in chronic myelomonocytic leukemia

A 59-year-old man with a six-month history of chronic myelomonocytic leukemia (CMML) was admitted to the Kitasato University Hospital because of melena in September 2000. Colonofiberscopy and barium enema demonstrated an ulcerated tumorous lesion in the transverse colon. The histopathologic findings of the ulcer bed revealed diffuse infiltration of granulocytes at each stage of differentiation. The diagnosis of granulocytic sarcoma (GS) was made. Surgical resection was not indicated, because thrombocytopenia was hardly improved enough to allow surgery despite repetitive transfusion of platelet concentrates. CMML developed to refractory anemia with excess of blast in transformation in February 2001. Two courses of low dose cytarabine plus aclarubicin were ineffective on the GS in spite of a decrease in the peripheral blood blasts. Progression to acute myeloid leukemia eventually broke out, in July 2001. The patient died of leukemia complicated with pneumonia and intestinal obstruction. At present, nine cases of GS in the colon have been reported. However, these cases did not include CMML. This is the first report describing GS in the colon associated with CMML.     

Cytogenetic risk stratification in chronic myelomonocytic leukemia

Background

The prognostic value of cytogenetic findings in chronic myelomonocytic leukemia is unclear. Our purpose was to evaluate the independent prognostic impact of cytogenetic abnormalities in a large series of patients with chronic myelomonocytic leukemia included in the database of the Spanish Registry of Myelodysplastic Syndromes.

Design and Methods

We studied 414 patients with chronic myelomonocytic leukemia according to WHO criteria and with a successful conventional cytogenetic analysis at diagnosis. Different patient and disease characteristics were examined by univariate and multivariate methods to establish their relationship with overall survival and evolution to acute myeloid leukemia.

Results

Patients with abnormal karyotype (110 patients, 27%) had poorer overall survival (P=0.001) and higher risk of acute myeloid leukemia evolution (P=0.010). Based on outcome analysis, three cytogenetic risk categories were identified: low risk (normal karyotype or loss of Y chromosome as a single anomaly), high risk (presence of trisomy 8 or abnormalities of chromosome 7, or complex karyotype), and intermediate risk (all other abnormalities). Overall survival at five years for patients in the low, intermediate, and high risk cytogenetic categories was 35%, 26%, and 4%, respectively (P<0.001). Multivariate analysis confirmed that this new CMML-specific cytogenetic risk stratification was an independent prognostic variable for overall survival (P=0.001). Additionally, patients belonging to the high-risk cytogenetic category also had a higher risk of acute myeloid leukemia evolution on univariate (P=0.001) but not multivariate analysis.

Conclusions

Cytogenetic findings have a strong prognostic impact in patients with chronic myelomonocytic leukemia.     

How I investigate chronic myelomonocytic leukemia

The 2016 revised 4th edition of the World Health Organization classification of hematopoietic neoplasms updated the diagnostic criteria for chronic myelomonocytic leukemia (CMML). Persistent peripheral blood monocytosis of at least 1 × 10⁹/L and a percentage of monocytes ≥10% of the circulating white blood cell count (WBC) are both prerequisite criteria for this diagnosis. CMML represents the prototype of “overlapping” myeloid neoplasms with concurrent myeloproliferative and myelodysplastic features. However, clinical presentation is heterogeneous, with cases showing prevailing “dysplastic” features and others a predominant “proliferative” phenotype. Accounting for this diversity, two variants of CMML are recognized: “dysplastic” CMML defined by WBC < 13 × 10⁹/L and “proliferative” CMML with WBC ≥ 13 × 10⁹/L often showing features mimicking a myeloproliferative neoplasm. Although not an official WHO category, the “oligomonocytic” variant of CMML is defined by relative monocytosis with an absolute monocyte count of 0.5‐0.9 × 10⁹/L. It can be considered a “pre‐phase,” as it frequently anticipates the development of an overt, classic CMML. In an attempt at improving disease prognostication, the blast count based grading system for CMML of the WHO 2008 Classification has been expanded in 2016 to include a new “CMML‐0” category. Lastly, the large body of knowledge on the molecular events occurring in CMML has been used to assist diagnosis and assess prognosis. Despite the step forwards, diagnosis of CMML still remains one of exclusion as no clinical, pathologic or molecular findings are specific for this disease. The current review brings insight into the spectrum of CMML and provides practical advice to approach suspected cases of CMML.     

Diabetes insipidus revealing chronic myelomonocytic leukemia

INTRODUCTION: Central diabetes insipidus is most frequently reported to occur after a trauma from surgery or accident. However, between 30 and 50% of cases are considered idiopathic. It's a rare complication of myelodysplastic syndrome. CASE REPORT: A 61-year-old patient presented central diabetes insipidus revealing, 17 months before, chronic myelomonocytic leukemia. Cytogenetics studies revealed monosomy 7. Acute myeloid leukemia appears 3 months after training rapid patient's death. DISCUSSION: Blood examination is necessary before to conclude idiopathic central diabetes insipidus. The discovery of chronic myelomonocytic leukemia implicates a rapid managing before its possible acute myeloid leukemia transformation. Indeed, prognosis of central diabetes insipidus and acute myeloid leukemia associated, in presence of monosomy 7, is very poor.     

Chronic lymphocytic leukemia coexisting with chronic myelomonocytic leukemia.

A case with coexisting chronic lymphocytic leukemia (CLL) and chronic myelomonocytic leukemia (CMML) is described. A 74-year-old man with a typical B-CLL also showed sustained peripheral blood and bone marrow monocytosis. Typical myelodysplastic changes and monosomy 7 were also found. Cytographic and immunophenotypic analysis confirmed the presence of two distinct cell populations, i.e., lymphoid and monocytoid. Both malignancies presented an extraordinarily benign prognosis. It remains uncertain whether monocytosis was either the expression of a distinct myelomonocytic clone or the progeny of a B/monocytic bipotential precursor able to feed both leukemic phenotypes.     

Novel therapeutic targets for chronic myelomonocytic leukemia

Chronic myelomonocytic leukemia (CMML) is a rare, age-related myeloid neoplasm with overlapping features of myelodysplastic syndromes/myeloproliferative neoplasms. Although gene mutations involving TET2, ASXL1 and SRSF2 are common, there are no specific molecular alterations that define the disease. Allogeneic stem cell transplant is the only curative option, with most patients not qualifying, due to advanced age at diagnosis and comorbidities. The only approved treatment options are hypomethylating agents; drugs that fail to alter the disease course or affect mutant allele burdens. Clinically CMML can be sub-classified into proliferative (pCMML) and dysplastic (dCMML) subtypes, with pCMML being associated with signaling mutations, myeloproliferative features, and a shorter overall survival. Given the paucity of effective treatment strategies there is a need for rationally informed and biomarker driven studies. This report will discuss current and prospective therapies for CMML and discuss the role for personalized therapeutics.     

Erythroid- and myeloid-lineage involvement in chronic myelomonocytic leukemia

Cell-lineage involvement in a typical case of chronic myelomonocytic leukemia (CMML) was examined by simultaneous analysis of morphology and chromosomes on the same single colonies. Cytogenetic analysis of patient's bone marrow cells showed two clones: 46,X,-Y,+M1 (63/68 cells) and 47,X,-Y,+M1,+M2 (5/68 cells). Bone marrow or peripheral blood mononuclear cells were plated at 1 X 10(4)/ml or 2 X 10(5)/ml (if thawed) in methylcellulose medium containing phytohemagglutinin-stimulated, leukocyte-conditioned medium and erythropoietin. On days 9-14 of culture, 68 single colonies were lifted and each colony served for both morphological and chromosome examination. Of the 68 colonies, 23 had two or more analyzable metaphases, yielding a total of 79 metaphases. Morphological examination revealed that 10 colonies contained macrophages (m), 10 had erythroblasts (E) and blasts (bl), and three had E, respectively. All of the single colonies were derived from abnormal clones, i.e., 22 (9m, 10b1E,3E) were from 46,X,-Y,+M1, and one (1m) was from 47,X,-Y,+M1,+M2. These findings demonstrate that erythroid and myeloid lineages are involved in CMML.