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

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