scholarly journals A Patient with Chronic Lymphocytic Leukemia, Chronic Myeloid Leukemia and Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-37
Author(s):  
Iolanda Donatella Vincelli ◽  
Patrizia Cufari ◽  
Carmelo Toscano ◽  
Al Sayyad Said ◽  
Mauro Campello ◽  
...  

Chronic lymphocytic leukemia (CLL) is an indolent lymphoproliferative disorder and is manifested by progressive accumulation of B cells in the blood, bone marrow and lymphatic tissues. Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disorder characterized by the presence of all the stages of myeloid development in the peripheral blood, and it is believed to be driven by the aberrant protein tyrosine kinase, a product of the mutant BCR-ABL1 gene.Multiple Myeloma (MM) is characterized by the accumulation of clonal plasmcells in the bone marrow with skeletal lesions, anemia, hypercalcemia and renal failure. Our patient is a 78 year-old man. In 2014 diagnosis of CLL and monoclonal gammopathy of undetermined significance (MGUS).At diagnosis: HB 13.5 g/dl; normal renal function;calcium 8.7 mg/dl;IgG 1678 mg/dl,serum immunoelectrophoresis: IgG kappa, Bence Jones kappa; total protein 7.5 g/dl, beta1 6,5%, beta2 24,1%;peripheral blood immunophenotyping showed CLL, FISH:negative;Cariotype: 46, XY; RX skeleton: positive for osteolytic lesions, total body TC scan: adenopathies of 18 mm and 15 mm at bilateral axillary level, norma spleen, adenopathy of 22 cm in the left obturator iliac region; presence of left hip prosthesis; bone marrow biopsy: localization by low-grade plasmacytoma.No CLL.The patient was only observed until April 2015, when there was a presence of myelocytes and metamyelocytes in peripheral blood and an increased spleen (18 cm). So he performed : bone marrow aspirate: diagnosis of CML (Sokal Score: 1,34 H; Eutos Score: 60 L, Hasford Score 1488,5);bone marrow biopsy: suggestive for a myeloproliferative disease (CML), MGUS with a modest lymphoid B component,BCR-ABL: 60;FISH: pathological presence of double fusion signal of the ABL1 and BCR loci in 209 of 271 interphase nuclei examined (77%).The patient started therapy with Imatinib, 400mg/die until July 2015, on the basis of the good response to treatment and the progressive increase of the M component that confirmed the progression to MM: Hb 9.1 g/dL, creatinine 1,1 mg/dl;calcium 10,5 mg/dl;total protein: 8,6 g/dl, gamma 48.02% (CM 4 gr); IgG 3536 mg/dl, cariotype: male with t (9; 22) and Philadelphia chromosome (25%);BCR-ABL: 14,32; bone marrow aspirate: plasmacells 15%;bone marrow biopsy: intermediate-interstitial plasmacytoma, CLL / lymphoma; RMN whole body: hyperintensity at the level of the seventh right rib; PET: osteolytic lesions of the side arch tenth right rib, right iliac bone, left iliac region, right tibia third diaphyseal.RX right hemithorax: osteolytic area at the level of the seventh right rib. So the patient started treatment with Bortezomib, Desamethasone, Alkeran (total 7 cycles).On March 2016, he performed a radiography that showed many osteolytic areas of 45 mm on third distal femur, third proximal and intermediate tibia, third proximal and third distal of fibula.A second PET documented a further MM progression due to new bone localizations and a left tibia biopsy showed localization disease. Radiotherapy colleagues have ruled out the usefulness of a radiation therapy program in consideration of the cerebral damage risk. On June 2016 the patient started a treatment with Lenalidomide for 15 days, interspersed by Glivec, maintaining the disease stable. In September 2017 he developed diplopia and with a nasal surgery, only inflammatory tissue was exported. A revision of the material confirmed plasmacytoma localization. In the same period appearance of a right gluteus sore treated initially with surgical dressing.As blood tests revealed increase of paraprotein levels, bone marrow biopsy resulted negative to myeloma and lymphoma diseases, instead a gluteal skin biopsy revealed plasmacytoma. It was decided to treat cerebral localization due to diplopia and peripherical paralysis. Radiotherapy was started on April 2018 (18 sessions). Bone marrow aspirate test showed plasmacells 15%, BCR-ABL dosage: 213,87, M component increase(5gr), IgG 4440 mg/dl, creatinine and serum calcium: normal. Due to disease progression, a rescue chemotherapy was started according to PAD protocol. After 4 cycles, a bone marrow aspirate documented the presence of plasmacells equal to 80%.The cytogenetic study confirmed the presence of a complex karyotype. So the patient started therapy with Daratumumab, Lenalidomide and Desamethasone which is currently ongoing with an excellent hematological and clinical response Disclosures Ciolli: Janssen: Honoraria; Abbvie: Research Funding.

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5301-5301
Author(s):  
Iolanda Donatella Vincelli ◽  
Patrizia Cufari ◽  
Said al Sayyad ◽  
Carmelo Tuscano ◽  
Natale Porta ◽  
...  

Abstract Metastatic disease of the bone is a rare complication of chronic lymphocytic leukemia (CLL), it may be result from richter's transformation or metastatic from non lymphoid malignancies. CLL is the most common form of adult leukemia, with the median age of 70 years at diagnosis [Siegel et al. 2013]. The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes.The result is the increased number of lymphocytes in the peripheral blood, leukocytosis with absolute lymphocytosis, the increase of the lymphnodes, the increase in size of the spleen. The diagnosis of chronic lymphocytic leukemia B requires the presence of Clonal B cells in the peripheral blood at or above 5,000 / ul for at least 3 months. Typing immunophenotypical pathological lymphocytes are positive for surface antigens CD5, CD19, CD23, weakly positive for CD20 and CD22, generally negative FMC7 and CD79b; also expressing surface immunoglobulins. The Rai and Binet staging systems, which are established by physical examination and blood counts, have been recognized as standards for deciding whether to begin treatment. Patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. For fit patients, chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab represents the current standard therapy. For unfit patients, treatment with an anti-CD20 antibody (obinutuzumab, rituximab, ofatumumab) plus a milder chemotherapy (Chlorambucil) may be applied. At relapse, if the treatment-free interval exceeds two to three years, the initial treatment may be repeated, if the disease relapses earlier, drugs such as bendamustine (plus rituximab), alemtuzumab, lenalidomide, ofatumumab, ibrutinib, or idelalisib, must be choosen. Patients with a del(17p) or TP53 mutation can be treated with ibrutinib or a combination of idelalisib and rituximab. in relapsing patients with TP53 mutations or del(17p) or patients that are refractory to repeated chemoimmunotherapies, an allogeneic SCT may be considered [Hallek M 2015]. In this article we show a case of a 66-year-old man with CLL and a bone localization. In 2011 diagnosis of CLL, Rai Stage 0, Binet Stage A. Principal characteristics at diagnosis: HB 13.2 g /dl, White Blood Cells 15.800 / mm3, lymphocytes 61%, neutrophils 32%, monocytes 4%, platelets 141.000/mm3; normal hepatic end renal function; flowcytometric immunophenotyping of the peripheral blood revealed B-cell CLL; prognostic factors: CD38 negative, ZAP70 positive, rearrangement of the immunoglobulins mutated; FISH: negative; CT chest / abdomen / pelvis: presence of multiple aorto-pulmonary and axillary adenopathies (max diameter of 2 centimeters); bone marrow biopsy: infiltration of CLL equal to 60% of global cellularity. The patient was only observed until January 2015, when he was hospitalized due to acute anemia, requiring supportive therapy, and right foot pain . So it was decided to re-evaluate the whole disease in order to decide whether to start chemotherapy. The disease was staged again with instrumental and laboratory tests: presence of renal insufficiency, egd and colonoscopy negative, Coombs' test negative, bone marrow biopsy confirmed the diagnosis of chronic lymphocytic with bone marrow infiltration of 90%, abdomen ultrasound showed only moderate splenomegaly. On February, persistence of right foot pain and appearance of swelling, assessed by the orthopedic as a suspected algic and dystrophic syndrome. So he suggested to perform scintigraphy which revealed: pronounced inflammatory osteometabolic reaction of the right tibia/fibula/ankle third distal which could be referred, in the first evaluation, to algic and dystrophic syndrome. However, a local biopsy was performed: localization of chronic lymphocytic leukemia. On March 2015 a total body TC showed 2 nodular calcifications in the right lung lobe, multiple right paratracheal, barety space, aortopulmonary and axillary adenopathies. Prostate size increased. In order to study carefully the liver and prostate lesions, an ultrasound abdomen was performed that documented only enlarged spleen, normal size liver, free of focal disease, increased prostate due to symmetric bilobate hypertrophy . After the second cycle of chemotherapy, prolonged thrombocytopenia, so he continues only with a radiotherapy program. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4583-4583
Author(s):  
Arthur Moellmann-Coelho ◽  
Luise Otero ◽  
Ricardo S. Bigni ◽  
Denise Azambuja ◽  
Claudio G. Stefanoff ◽  
...  

Abstract We describe the clinical, cytogenetic, hystopathologic, immunophenotypic and molecular findings of a rare case of Philadelphia positive chronic myeloid leukemia (Ph+ CML) and B-cell chronic lymphocytic leukemia (B-CLL) occurring simultaneously at diagnosis, in a 57-year-old female patient. In the present case, the patient showed at diagnosis leukocytosis (48.000/ul) with myelocytes and metamyelocytes along with well-differentiated neutrophils, but also with well differentiated lymphocytosis (28.992/ul) in peripheral blood (PB) and also in bone marrow (BM) aspirate cytology. FACS cytometry exhibited clearly two predominant separated cellular populations and the immunophenotype profile of the lymphoid component in BM and PB was CD5+, CD20+, CD23+, with light chain clonal restriction. The BM hystopathological analysis showed two distinct cellular populations, one lymphoid well differentiated CD5+/CD20+, and other myeloid, in several stages of differentiation. Cytogenetic analysis with unstimulated bone marrow culture confirmed the presence of Philadelphia chromosome but with additional translocation involving chromosomes 9, 10 and 22. Molecular studies showed the evidence of BCR-ABL positivity and the B-cell clone was documented by the presence of a clonal heavy chain immunoglobulin rearrangement. The patient was treated with imatinib mesylate 400mg/day, achieving complete cytogenetic response at the fourth month, and complete molecular response (nested PCR) of the BCR-ABL component at the sixth month of treatment. Besides, the absolute lymphocytosis was gradually reduced during the treatment exclusively with imatinib, achieving normal absolute values at the sixth month. This seldom described case of simultaneous occurrence of these two rare chronic hematological malignancies, brings interesting questions about the possible cellular origin and the correspondent mechanisms of clonal expansion. The therapeutic response of the B-cell lymphoid clone exhibited, brings also a possible relationship with the observation that the c-Abl could have enhanced expression in B-CLL cells, as described by Ke Lin et al, in which the c-Abl kinase activity could be inhibited by imatinib mesylate.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4421-4421
Author(s):  
Krystyna M Zawilska ◽  
Lucyna Malendowicz-Portala

Abstract Abstract 4421 The coexistence of B-cell chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) in the same patient is rare. A 61-year-old man developed a lymphocytosis with morphologic and immunophenotypic feature of B-CLL (stage I according to the modified Rai classification), without indications for treatment. Ten months later he presented with a markedly elevated leukocytes count and splenomegaly. Myeloblasts, promyelocytes, myelocytes and metamyelocytes appeared in his peripheral blood. A bone marrow aspirate was hypercellular with an increased proportion of the myeloid series in all maturative stages; the percentage of lymphocytes was 3%. The immunophenotypic study demonstrated the typical feature of chronic phase of CML, simultaneously 2% of CD5+ CD19+ cells have been found. Unstimulated bone marrow culture shoved a 46,XY,t(9;22)(q34;q11.2) karyotype, and interphase FISH detected the presence of BCR/ABL fusion with 4,55×106 of p 210 and 1,55×103of p 190 copies/ml. Previously it has been shown that these two different hematological malignancies derive from distinct progenitors. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
1990 ◽  
Vol 76 (11) ◽  
pp. 2337-2342
Author(s):  
IM Clauss ◽  
B Vandenplas ◽  
MG Wathelet ◽  
C Dorval ◽  
A Delforge ◽  
...  

Recombinant human interferon-alpha (IFN-alpha) can induce a hematologic remission in patients with chronic myeloid leukemia. However, some patients are resistant and others develop late resistance to the IFN- alpha treatment. To understand the molecular mechanism of this resistance, we have analyzed the expression of 10 IFN-inducible genes in the cells of three resistant patients, two responsive patients, and six healthy controls. Northern blot hybridizations showed that all the genes were induced in in vitro IFN-alpha treated peripheral blood cells of the patients and healthy controls. These genes were also inducible in peripheral blood and bone marrow cells of two out of two resistant patients administered an injection of IFN-alpha. We conclude that the resistance to the IFN-alpha treatment of the chronic myeloid leukemia patients we studied is not due to (1) the absence of induction of any of the 10 IFN-inducible genes we studied, including the low-molecular- weight 2′-5′oligoadenylate synthetase; (2) the presence of an antagonist of IFN-alpha in the peripheral blood or bone marrow cells; and (3) the presence of neutralizing anti-IFN-alpha antibodies.


2018 ◽  
Vol 140 (2) ◽  
pp. 105-111 ◽  
Author(s):  
Fiorina Giona ◽  
Michelina Santopietro ◽  
Giuseppe Menna ◽  
Maria Caterina Putti ◽  
Concetta Micalizzi ◽  
...  

Background: To date, no data on the adherence to specific guidelines for children with chronic myeloid leukemia (CML) in chronic phase (CP) have been reported. Methods: Since 2001, guidelines for treatment with imatinib mesylate (IM) and monitoring in patients younger than 18 years with CP-CML have been shared with 9 pediatric referral centers (P centers) and 4 reference centers for adults and children/adolescents (AP centers) in Italy. In this study, the adherence to these guidelines was analyzed. Results: Thirty-four patients with a median age of 11.4 years and 23 patients with a median age of 11.0 years were managed at 9 P and at 4 AP centers, respectively. Evaluations of bone marrow (BM) and/or peripheral blood (PB) were available for more than 90% of evaluable patients. Cytogenetics and molecular monitoring of PB were more consistently performed in AP centers, whereas molecular analysis of BM was carried out more frequently in P centers. Before 2009, some patients who responded to IM underwent a transplantation, contrary to the guidelines’ recommendations. Conclusions: Our experience shows that having specific guidelines is an important tool for an optimal management of childhood CP-CML, together with exchange of knowledge and proactive discussions within the network.


2000 ◽  
Vol 124 (9) ◽  
pp. 1361-1363
Author(s):  
Anwarul Islam ◽  
Adrian O. Vladutiu ◽  
Theresa Donahue ◽  
Selina Akhter ◽  
Amy M. Sands ◽  
...  

Abstract The expression of CD8, a restricted T-cell antigen, on B cells in B chronic lymphocytic leukemia is rare, and its significance, if any, remains unknown. We report herein a patient with B chronic lymphocytic leukemia in whom CD8 was strongly expressed on all B cells, both in the bone marrow and peripheral blood. The patient required no therapy for 6 years after being diagnosed as having B chronic lymphocytic leukemia. Then, when the disease progressed, he was treated with conventional doses of fludarabine phosphate (25 mg/m2 daily for 5 days), but unlike other patients with B chronic lymphocytic leukemia he tolerated this therapy poorly. He received a total of only 4 series of fludarabine therapy, and following each course of treatment, he developed considerable myelosuppression. After the fourth course of therapy, his bone marrow failed to show any evidence of regeneration, and he died as a result of intercurrent respiratory tract infection 1 month after his last dose of fludarabine was given.


Blood ◽  
1978 ◽  
Vol 52 (1) ◽  
pp. 255-260 ◽  
Author(s):  
R Hoffman ◽  
S Kopel ◽  
SD Hsu ◽  
N Dainiak ◽  
ED Zanjani

Abstract The pathogenesis of the anemia associated with malignancy was investigated in a patient with T cell chronic lymphocytic leukemia. The plasma clot culture system was used as a measure in vitro of erythropoiesis. The patient's peripheral blood and marrow T lymphocytes obtained both before and after transfusion therapy suppressed erythroid colony formation by normal human bone marrow cells. Pretreatment of the patient's bone marrow T cells by antithymocyte globulin (ATG) and complement reversed this suppression. In addition, pretreatment of the patient's marrow cells with ATG and complement markedly augmented erythropoiesis in vitro. The expression of erythroid activity caused by the selective destruction of the suppressor T lymphocytes in the patient's bone marrow with ATG and the suppression of normal erythropoiesis by the patient's bone marrow and peripheral blood lymphocytes suggest that interaction between the malignant T cell and the erythropoietin-responsive stem cell is important in production of anemia in this patient.


2019 ◽  
Vol 12 ◽  
pp. 1179545X1989457
Author(s):  
Tahseen Hamamyh ◽  
Mohamed A Yassin

Autoimmune hemolytic anemia is one of the differential diagnoses for anemia in patients with lymphoproliferative neoplasia, such as chronic lymphocytic leukemia, who experience sudden drop in hemoglobin. The association between autoimmune hemolytic anemia and chronic myeloid leukemia on the contrary is unusual. Here we present a patient with a background of chronic myeloid leukemia treated previously with Tyrosine Kinase Inhibitors, then developed autoimmune hemolysis simultaneously with chronic myeloid leukemia relapse. Hemolysis was treated with steroids with good response.


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