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Hairy cell leukemia in kidney transplantation: lesson from a rare disorder.

Vinante F, Tomei P, Zaza G, Zamò A, Lupo A - Exp Hematol Oncol (2013)

Bottom Line: We report here on the diagnosis and successful treatment of a case of hairy cell leukemia (HCL) that arose 15 years after kidney transplantation in a 51-year-old patient.Recently, however, the oncogenic mutation V600E of the BRAF protein kinase has been found to be a hallmark of HCL, and calcineurin inhibitors have been shown to interfere with signaling downstream of V600E BRAF early on by counteracting senescence-associated mechanisms that protect against the oncogenic potential of the mutated kinase.This mechanism might also be involved in other neoplasias bearing the same or similar mutations, such as melanoma and non-melanoma skin cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Section of Hematology, Department of Medicine, University of Verona, Verona, Italy.

ABSTRACT
We report here on the diagnosis and successful treatment of a case of hairy cell leukemia (HCL) that arose 15 years after kidney transplantation in a 51-year-old patient. As soon as the diagnosis was made, HCL was treated with 2-CDA, obtaining complete hematological remission. Immunosuppression with the calcineurin inhibitor cyclosporin was maintained, and the graft was preserved. In kidney transplant recipients supported with immunosuppressive drugs, post-transplant lymphoproliferative diseases (PTLDs) are frequent and typically related to immunosuppression via a loss of control of infectious/EBV-related proliferative stimuli. To date, HCL has not been considered among PTLDs. Recently, however, the oncogenic mutation V600E of the BRAF protein kinase has been found to be a hallmark of HCL, and calcineurin inhibitors have been shown to interfere with signaling downstream of V600E BRAF early on by counteracting senescence-associated mechanisms that protect against the oncogenic potential of the mutated kinase. Such a biochemical link between the oncogene-dependent signaling and calcineurin inhibitor activities suggests that HCL in transplanted patients might be a peculiar type of PTLD based on the presence of a specific mutation. This mechanism might also be involved in other neoplasias bearing the same or similar mutations, such as melanoma and non-melanoma skin cancer.

No MeSH data available.


Related in: MedlinePlus

Sequential hemochrome and creatinine values in relationship to treatment.
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Figure 2: Sequential hemochrome and creatinine values in relationship to treatment.

Mentions: The severely neutropenic patient was supported with both G-CSF and Epo and underwent ambulatory chemotherapy with the purine analog 2-CDA (2-Chlorodeoxyadenosine, leustatin, cladribine) according to a schedule of 0.1 mg/Kg IV once per week for 4 to 6 weeks. Prophylaxis with sulfamethoxazole-trimethoprim and recommended adequate hydration with crystalloids were performed. The 2-CDA schedule was continued for up to 6 administrations without adverse reactions or infectious complications. Due to an increase in serum creatinine to 199 μmol/L, the fourth administration was delayed one week, and the entire course of therapy lasted 7 weeks. Blood counts reached normal values approximately 2 months after starting 2-CDA. Currently, one year after stopping treatment, the patient is in continuous complete hematological remission with stable renal function (Figure 2). No bone marrow evaluation was performed.


Hairy cell leukemia in kidney transplantation: lesson from a rare disorder.

Vinante F, Tomei P, Zaza G, Zamò A, Lupo A - Exp Hematol Oncol (2013)

Sequential hemochrome and creatinine values in relationship to treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750510&req=5

Figure 2: Sequential hemochrome and creatinine values in relationship to treatment.
Mentions: The severely neutropenic patient was supported with both G-CSF and Epo and underwent ambulatory chemotherapy with the purine analog 2-CDA (2-Chlorodeoxyadenosine, leustatin, cladribine) according to a schedule of 0.1 mg/Kg IV once per week for 4 to 6 weeks. Prophylaxis with sulfamethoxazole-trimethoprim and recommended adequate hydration with crystalloids were performed. The 2-CDA schedule was continued for up to 6 administrations without adverse reactions or infectious complications. Due to an increase in serum creatinine to 199 μmol/L, the fourth administration was delayed one week, and the entire course of therapy lasted 7 weeks. Blood counts reached normal values approximately 2 months after starting 2-CDA. Currently, one year after stopping treatment, the patient is in continuous complete hematological remission with stable renal function (Figure 2). No bone marrow evaluation was performed.

Bottom Line: We report here on the diagnosis and successful treatment of a case of hairy cell leukemia (HCL) that arose 15 years after kidney transplantation in a 51-year-old patient.Recently, however, the oncogenic mutation V600E of the BRAF protein kinase has been found to be a hallmark of HCL, and calcineurin inhibitors have been shown to interfere with signaling downstream of V600E BRAF early on by counteracting senescence-associated mechanisms that protect against the oncogenic potential of the mutated kinase.This mechanism might also be involved in other neoplasias bearing the same or similar mutations, such as melanoma and non-melanoma skin cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Section of Hematology, Department of Medicine, University of Verona, Verona, Italy.

ABSTRACT
We report here on the diagnosis and successful treatment of a case of hairy cell leukemia (HCL) that arose 15 years after kidney transplantation in a 51-year-old patient. As soon as the diagnosis was made, HCL was treated with 2-CDA, obtaining complete hematological remission. Immunosuppression with the calcineurin inhibitor cyclosporin was maintained, and the graft was preserved. In kidney transplant recipients supported with immunosuppressive drugs, post-transplant lymphoproliferative diseases (PTLDs) are frequent and typically related to immunosuppression via a loss of control of infectious/EBV-related proliferative stimuli. To date, HCL has not been considered among PTLDs. Recently, however, the oncogenic mutation V600E of the BRAF protein kinase has been found to be a hallmark of HCL, and calcineurin inhibitors have been shown to interfere with signaling downstream of V600E BRAF early on by counteracting senescence-associated mechanisms that protect against the oncogenic potential of the mutated kinase. Such a biochemical link between the oncogene-dependent signaling and calcineurin inhibitor activities suggests that HCL in transplanted patients might be a peculiar type of PTLD based on the presence of a specific mutation. This mechanism might also be involved in other neoplasias bearing the same or similar mutations, such as melanoma and non-melanoma skin cancer.

No MeSH data available.


Related in: MedlinePlus