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Older and unfit patients with Acute Myeloid Leukemia (AML), which are uneligible for standard induction therapy, have limited treatment options. The therapeutic approach in these cases is based on the use of hypomethylating agents, either decitabine or azacitidine, or Low-Dose Cytarabine (LDAC). However, despite the extensive use of these agents, there is no consensus regarding the extent of their efficacy, and clinical benefit deriving from their use is very modest. We present a case of FLT3- and TP53-mutated AML in an unfit patient with congenital agammaglobulinemia, responsive to single agent decitabine, with a response duration of over 20 months.

Currently, the prognosis of Ph+ acute lymphoblastic leukemia (Ph+ ALL) patients relapsing after an allogenic hematopoietic stem cell transplantation (allo-SCT) remains poor, with few therapeutic options available. Here we present the case of a 32 years old patient with dasatinib-resistant post-transplant molecular relapse of ALL, who received, as second-line therapy, the combination of ponatinib and donor lymphocyte infusion (DLI). The therapy was safe and the patient achieved a sustained minimal residual disease negative disease, still ongoing after 22 months, which was accompanied by several changes in the immune populations distribution within the bone marrow (i.e., the increase in the CD8/CD4 lymphocytes ratio). Our report provides evidence of the efficacy of the third generation TKI inhibitor ponatinib in combination with DLI as second line therapy for Ph+ ALL relapsing after an allo-SCT.

We report a case of a chronic myeloid leukemia patient showing progressive bone marrow fibrosis and anemia during imatinib therapy. Given the loss of major molecular response, we switched treatment to dasatinib 100 mg daily, observing a reduction in BCR-ABL transcript, a significant improvement of anemia, and a gradual disappearance of fibrosis. After 7 years of dasatinib therapy the patient maintains a complete cytogenetic response and a deep molecular response; the last bone biopsy confirmed the absence of fibrosis.

The clinical outcome of elderly patients with Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) has significantly improved following targeted treatment with tyrosine-kinase inhibitors (...

We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecular response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i.v., days 1-5, cyclophosphamide 700 mg i.v., days 1-5, and ponatinib 45 mg p.o., daily starting at day 15). We observed a rapid decrease in minimal residual disease on molecular assessment with an MMR of P190-BCR-ABL/ABL = 0.01% confirmed by bone marrow revaluations at days +23, +59, +108, and +191 after the first day of salvage chemotherapy. After starting ponatinib, the patient experienced skin graft-versus-host disease, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib treatment was well tolerated and considered safe with easily manageable side effects.

Autoimmune hemolytic anemia (AIHA) is a rare and potentially life-threatening event which may complicate the course of chronic lymphocytic leukemia (CLL) at any time and steroid-refractory AIHA of CLL poses a therapeutic challenge for physicians. Here, we report the safety and efficacy of a rituximab-containing regimen in a CLL patient with steroid- and IVIg-refractory AIHA.A 57-year- old man affected by CLL, presented with fatigue, dyspnoea, tachycardia and jaundice. His physical examination revealed overt jaundice, hepato- and splenomegaly, and enlargement of lymph nodes in all superficial sites. The blood chemistry showed severe anemia (Hb value 3.9 g/dL), high white blood cell count (89 x 10(9)/L), altered hemolysis markers and direct antiglobulin test (DAT) was positive for both complement and IgG. The patient failed to respond to both a 4-day course of high-dose dexamethasone IV (40 mg/day) and intravenous immunoglobulin (IVIg) (1 g/kg/day x 2 days). Thus, a schedule containing rituximab (375 mg/m(2) day +1), cyclophosphamide (750 mg/m(2) day +2) and prednisone (60 mg/m(2) from day +1 to day +7) (R-CP) were administered. Four cycles, repeated every 4 weeks, were administered. After 4 days from the infusion of this schedule, the patient showed a marked reduction of the lymphocytosis, and the hemoglobin level started to increase. No rituximab-related side effects were recorded. At the end of treatment DAT became negative and patient achieved a nodular Partial Remission (nPR).Our data showed the safety and efficacy of a rituximab-containing regimen in a life-threatening CLL-related AIHA, refractory to steroid and IVIg therapy. This schedule has allowed the patient to obtain a prompt and dramatic rise in hemoglobin level and a response to both AIHA and CLL.