Interferon-beta induced remission in a hairy cell leukemia patient resistant to interferon-alpha

Two patients with advanced hairy cell leukemia and pancytopenia responded successfully to intramuscular injections of recombinant interferon-beta, with normalisation of blood counts. One of the patients had developed resistance to interferon-alpha. The in-vivo response was predicted by in-vitro studies showing a beneficial effect of IFN-beta on erythropoiesis in cell cultures derived from these patients.     

Chemotherapy-induced remission in a patient with small cell carcinoma of the lung and hairy cell leukemia

Small cell carcinoma of the lung developed in a patient with previously diagnosed hairy cell leukemia. Treatment with aggressive chemotherapy resulted in a complete response in both diseases lasting 13 months. Recurrence of the leukemia did not occur. This case demonstrates that hairy cell leukemia may be responsive to combination regimens.     

Anaplastic neoplasm in a patient with hairy cell leukemia

A 63-year-old white man had a history of recurrent pneumonia, pancytopenia, and splenomegaly when the diagnosis of hairy cell leukemia was made on bone marrow biopsy examination. Splenectomy confirmed that diagnosis and his pancytopenia moderately improved. Three years following the diagnosis, the patient developed an upper abdominal mass involving the stomach wall that was found to be an anaplastic "large cell" neoplasm. Palliative radiotherapy was started, but the patient died 2 months later. Cytochemical studies of the anaplastic gastric neoplasm revealed cytoplasmic tartrate resistant acid phosphatase activity. Electron microscopy showed no epithelial differentiation. These observations suggest that the gastric neoplasm represented an evolution of hairy cell leukemia into a more aggressive tumor analogous to the transformation that occurs in other B-cell neoplasms.     

Severe Legionella pneumophila infection in a patient with hairy cell leukemia in partial remission after alpha interferon treatment

Legionella pneumonia is an increasingly frequently reported complication in immunocompromised patients, particularly patients with hairy cell leukemia (HCL) in active phase. The most important predisposing factor seems to be the quantitative and qualitative defect of the monocytic-macrophagic system characteristic of HCL. We report a case of severe Legionella pneumophila infection with multisystem involvement in a patient with HCL in stable partial remission obtained after therapy with interferon. In our patient recovery of a normal monocyte count did not protect against a legionella infection, indicating that this pathogen should always be sought in HCL patients even those in clinical and hematologic remission. Early diagnosis and appropriate treatment may reduce the mortality of this serious complication.     

Leukemic meningitis in a patient with hairy cell leukemia. A case report

Central nervous system involvement has not previously been described in patients with hairy cell leukemia (HCL). A patient is reported who presented with meningeal involvement as his initial symptom of HCL. Diagnosis was established by morphologic and cytochemical studies of his cerebrospinal fluid (CSF) and bone marrow. Treatment with whole-brain irradiation and intrathecal chemotherapy was successful in clearing leukemic cells from the CSF with resolution of symptoms.     

The relapse of hairy cell leukemia after a 32-year remission

The optimum therapy for hairy cell leukemia (HCL) is controversial. Dramatic responses to interferon-alpha and 2'-deoxycoformycin overshadow the established role of splenectomy in HCL, and patients currently can avoid surgery altogether. A case is presented of clinical remission lasting 32 years after splenectomy--a prolonged normal life, without medication or medical intervention. When relapse occurred, the patient's response to interferon-alpha was prompt and predictable. Prognostic variables are an important consideration at the time of diagnosis in predicting the response to splenectomy.     

Sezary cells with hairy projections

A case of sezary syndrome where the sezary cells showed cytoplasmic hairy projections is reported. The patient had typical exfoliative erythematous dermatitis, high white cell count, atypical lymphocytes of T-phenotype with folded nuclei and bone marrow involvement. The ultra structure study showed cerebriform nucleus and cytoplasmic projections.     

Myelodysplasia terminating in acute myeloid leukemia in a hairy cell leukemia patient treated with 2-deoxycoformycin

Purine analogs are effective in the treatment of several chronic lymphoproliferative disorders (CLPD) including hairy cell leukemia (HCL). To date, little evidence exists that these drugs are oncogenic. We report a case of HCL in a 66-year-old male treated with 2-deoxycoformycin. Just over 1 year following completion of his treatment, falling platelet and white cell counts were associated with the development of dysplastic features in his bone marrow and a rising blast cell count, culminating in the development of acute myeloid leukemia (AML). To the best of our knowledge only two previous cases of AML have been linked to treatment of HCL with purine analogs, both with 2-chlorodeoxyadenosine. We emphasize the need for long term follow up of patients treated with purine analogs and suggest that even those who are apparently cured be monitored periodically.     

Development of hairy cell leukemia in a patient after cardiac transplantation

Post-transplant lymphoproliferative disorders (PTLDs) are well-recognized complications of bone marrow and solid organ transplantation, comprising a heterogenous group of lymphoproliferations with a spectrum of morphologic, phenotypic and molecular features. Although PTLDs are usually Epstein-Barr virus-driven B-cell lymphoproliferations, T/natural killer-cell lymphoproliferations, multiple myeloma, and Hodgkin's lymphoma are also recognized as part of the PTLD spectrum. Hairy cell leukemia, a low-grade B-cell lymphoproliferation, has not been recognized as part of the PTLD spectrum. We report the first case of hairy cell leukemia occurring after cardiac transplantation. It is unclear whether this case, similar to other cases of low-grade B-cell lymphoproliferations reported after transplantation, is related to immunosuppression and therefore part of the spectrum of PTLDs, or merely represents coincidental event occurring in an immunocompromised patient.     

Cryocrystalglobulinemia in hairy cell leukemia.

A patient with hairy cell leukemia (leukemic reticuloendotheliosis) was noted to have a spurious leukocytosis caused by a spontaneously crystallizing cryoglobulin. The cryoprotein was identified as IgG lambda. An intracytoplasmic immunoglobulin demonstrable within the hairy cell was also IgG lambda. The cryoglobulin spontaneously disappeared over a four day period. A reliable automated count on the Coulter Model S could be obtained by prewarming the blood specimen to 37 C.     

Successful treatment of extranodal Hodgkin's lymphoma in a patient with longstanding hairy cell leukemia

Purine analogs, particularly pentostatin and cladribine, are highly effective in hairy cell leukemia (HCL). Both of these drugs induce responses in approximately 80 - 95% of patients. However, it is not yet determined if treatment with these drugs can induce second malignancies. Hodgkin's lymphoma is very rare as a second malignancy and there are only 3 reported cases concerning the association of this lymphoma with HCL. We describe a patient with longstanding HCL in complete remission after cladribine, in whom extranodal Hodgkin's lymphoma appeared 8 years after the diagnosis of HCL. Magnetic resonance imaging revealed diffuse intra-osseal neoplastic infiltration of the corpora of the whole spinal column and extra-osseal propagation from the fifth thoracic vertebra into the spinal canal with spinal cord compression. Histological and immunohistochemical analysis of the extradural tumor, which was completely excised, disclosed nodular sclerosis Hodgkin's lymphoma with typical Reed - Sternberg cells that were positive for CD30, CD15, bcl-6, Ki67, p53, EBV LPM-1 and IgG, and negative for CD45, CD20, DBA44, kappa, lambda light chains and IgM. In addition, immunohistochemical analysis of the bone marrow in 1999 showed infiltration with positivity for IgM and negative for kappa light chains and IgG. These findings (expression of different immunoglobulins and light chains on the cells) suggest an independent origin of these 2 B-cell neoplasms. After neurosurgery the patient received 6 courses of the MP-ABVD protocol and achieved a complete remission, which has lasted 16 months thus far.     

Development of hairy cell leukemia in a patient treated with cytoreductive agents for essential thrombocythemia

The association of second malignancies in hairy cell leukemia (HCL) is well recognized. Most of these malignancies are either solid tumors or lymphoproliferative disorders rather than myeloproliferative disorders. But these malignancies are usually related to a complication of the drug treatment for HCL. The chronological sequence of HCL occurring after a hematological disorder is very rarely described. This report describes the first case, to our knowledge, of a patient who developed HCL five years after essential thrombocythemia that was treated with oral cytoreductive agents. Pathogenesis of the coexistence of both diseases is discussed.     

Current treatment options in hairy cell leukemia and hairy cell leukemia variant

Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder characterized by splenomegaly, pancytopenia and circulating lymphocytes displaying prominent cytoplasmic projections. HCL has usually an indolent course and the patients with asymptomatic disease do not require therapy. Treatment of progressive symptomatic HCL includes a variety of pharmacological approaches such as interferon-alpha (IFN-alpha), pentostatin (DCF) and cladribine (2-CdA), which have significantly improved the disease prognosis. 2-CdA and DCF seem to induce a similar high response rate and a long overall survival. They are also active in relapsed patients. More recently high activity of anti-CD20 monoclonal antibody (rituximab) and anti-CD25 (LMB-2) and anti-CD22 (BL-22) immunotoxins have increased the number of therapeutic options for HCL. Splenectomy may be still indicated in patients with massive, symptomatic splenomegaly or results in severe cytopenia. IFN-alpha may have a place in patients with very severe cytopenia, in HCL in pregnancy and in patients who have failed prior therapy with purine nucleoside analogs. HCL variant (HCL-V) is a distinct clinico-pathological entity which seems to be resistant to IFN-alpha and purine nucleoside analogs - DCF and 2-CdA. However, preliminary observations suggest that monoclonal antibodies - rituximab and BL-22 immunotoxin are highly active in this disorder even refractory to 2-CdA. In this review current therapeutic strategies in HCL and HCL-V are presented.     

Cladribine in hairy cell leukemia

Cladribine results in prolonged complete remissions in most patients wo have HCL. Several studies have indicated that patients who are in complete remission have survivals that are comparable to those of normal age-matched controls. HCL-related mortality is distinctly uncommon. Nevertheless, it is unlikely that cladribine treatment of HCL is curative because MRD is common in the bone marrows of complete responders. Response criteria for HCL include clinical, hematologic, and morphologic criteria, but do not include flow cytometry, immunohistochemical analysis, or molecular studies. More sensitive techniques have been used by Filleul and colleagues to detect MRD. The used clonoegenic probes from the hypervariable regions of the immunoglobulin heavy-chain gene and performed polymerase chain reactions (PCRs) on bone marrow biopsy specimens, All seven patients who were in morphologic complete remission after a single cladribine infusion were PCR positive. These data indicate that cladribine induces protracted remissions but is not necessarily curative. MRD can be detected in most patients when sensitive techniques are used. Persistence of immunohistochemical MRD may predict detected MRD remains to be studied in a large number of patients. Investigators from the University of Pisa in Italy have used a combination of cladribine and rituximab to eradicate MRD in patients who have HCL. Ten patients received treatment with a standard infusion of cladribine. Two patients achieved a complete remission, 6 patients achieved a partial remission, and 2 patients failed to respond. All were PCR positive for the immunoglobulin heavy-chain (IgH) gene product at the completion of cladribine treatment. All 10 patients had achieved a complete hematologic response 2 months after the completion of ritximab therapy. The curative nature of this treatment will require long-term follow-up. Cladribine represents a major therapeutic advance in the treatment of HCL. The prognosis of patients who have HCL has improved greatly with cladribine therapy. Future strategies should address combination therapy with purine analogs and monclonal antibodies. These strategies should address eradication of MRD in an attempt to develop a potentially curative combination treatment program.     

DNA-abnormality in hairy cell leukemia

Spleen and light density peripheral blood leukocytes of 10 hairy cell leukemia (HCL) patients and total leukocytes of one patient and blood donor cells were stained quantitatively for cellular DNA. The DNA content of single cells was measured by flow cytometry (FC) and compared to the DNA content of sheep cells admixed as an internal control. Eight of eleven patients (72 per cent) showed deviations from blood donor DNA content. Two female patients showed increased cellular DNA content, the six male patients had hypodiploid cells. Chromosomal aberrations are therefore likely to exist in the majority of HCL patients. Separation of HCL cells into sheep erythrocyte rosette and non rosette forming cells revealed similar DNA abnormalities in both cell populations, suggesting that the leukemia encompasses cells with B and with T markers.     

Lymphomatoid granulomatosis in a patient with acute myeloblastic leukemia in remission

In a patient treated for acute myeloblastic leukemia (AML), we saw an angiocentric and angiodestructive lymphoma that resembled lymphomatoid granulomatosis (LG). The lesions tended to involve extranodal sites such as the lung, the parotid gland, and the skin. The immunologic studies showed that the proliferating lymphoid cells were mature T cells. Furthermore, genotypic studies disclosed a clonal rearrangement of the beta T-cell receptor gene. It is concluded that this case of LG is related to a neoplastic T-cell lymphoproliferative disorder. The relations between LG and the previous AML are discussed.     

Genotypic and phenotypic evidence of T-cell leukemia in a patient successfully treated by interferon-alpha for typical hairy cell leukemia.

A 53-year-old man was diagnosed to have typical hairy cell leukemia. Immunophenotyping of frozen splenic tissue showed clonality of hairy cells for mu lambda, confirmed by the corresponding immunoglobulin gene rearrangements. The patient was successfully treated with interferon-alpha (IF-alpha). In the fifth year of treatment with IF-alpha the morphology of peripheral blood mononuclear cells (PBMC) and of bone marrow infiltration changed with the appearance of numerous small to intermediate shaped lymphocytes of a T-helper phenotype. Frank leukemia, resistant to IF-alpha treatment and ultimately aggressive chemotherapy, developed. Emergence of this second clonal disease was confirmed by rearrangement studies performed on PBMC; rearrangements of both alleles of the TCR beta were identified, whereas the JH and lambda IVS genes were in germline configuration. The outgrowth of a second, malignant T-cell clone paralleled by the disappearance (down-regulation?) of the initial B-cell clone while under cytokine treatment is consistent with the possibility that IF-alpha favoured the emergence of this second clone.