European-American-type hairy cell leukemia without splenomegaly, treated successfully with deoxycoformycin]

A 55-year-old Japanese man was hospitalized on October 5, 1999, because of high fever. Physical examination revealed neither lymphadenopathy nor hepato-splenomegaly. Laboratory data on admission showed a white blood cell count of 1,580/microliter, a hemoglobin level of 9.1 g/dl, and a platelet count of 113 x 10(3)/microliter. A small percentage of abnormal mononuclear cells were present in the peripheral blood. A bone marrow biopsy specimen demonstrated myelofibrosis and diffuse infiltration of abnormal monoculear cells with a mature B cell phenotype. A bone marrow aspirate showed 29% abnormal mononuclear cells, which had an indented or folded nucleus and reticular nuclear chromatin. Moderate to strong tartarate-resistant acid phosphatase activity was detected in these cells. Although the cytoplasmic projections were poorly preserved in specimens stained with May-Giemsa, fresh preparations showed numerous slender cytoplasmic projections by phase-contrast microscopy. The hairy cells had the phenotype CD5-, CD10-, CD11c+, CD19+, CD20+, CD25+, lambda. The patient was diagnosed as having European-American-type hairy cell leukemia (HCL) without splenomegaly, which is quite rare in Japan. The value of phase-contrast microscopy for recognition of the hairy cells was emphasized. The patient was treated successfully with deoxycoformycin (DCF).     

Sequential administration of recombinant interferon alpha and deoxycoformycin in the treatment of hairy cell leukaemia.

Both recombinant interferon alpha and deoxycoformycin (dCF) are effective in the treatment of hairy cell leukaemia. In an attempt to reduce the complications from dCF therapy, a pilot study of the Eastern Cooperative Oncology Group (ECOG) first treated patients with interferon to improve peripheral blood cell counts before dCF treatment began. Thirty-four patients were treated for 3 months with recombinant interferon alpha-2a (rIFN alpha-2a), 3 x 10(6) IU subcutaneously three times a week for 3 months, and then by dCF, 4 mg/m2 intravenously every 2 weeks for a maximum of 12 months. The overall response rate was 94% (32/34); 76% of patients (26/34) had complete response (CR) (90% confidence interval, 62-88%) and 18% (6/34) partial response. One patient was found to have a Mycobacterium avium infection while receiving rIFN alpha-2a. Without specific antimycobacterial therapy and with continued administration of rIFN alpha-2a and dCF, the infection resolved and he achieved CR. Three patients had culture-negative febrile episodes during the dCF phase of treatment. Non-disseminated herpes zoster developed in four patients, but three of the episodes occurred only after treatment was discontinued. Sequential administration of rIFN alpha-2a and dCF resulted in fewer infections (P = 0.027) than in ECOG's previous study of dCF used alone. Two patients died, one of combined hairy cell leukaemia and non-Hodgkin's lymphoma of intermediate histologic type 17 months after entry into the study and the other of cardiac arrest 20 months after entry. Thirty-two patients were alive with a median follow-up of 21 months (range 13-31 months). This combination produces durable CRs with a low incidence of infection.     

Successful treatment of hairy cell leukemia with pentostatin

A 45-year-old woman was admitted to our hospital in August, 1999. Laboratory data showed a white blood cell count of 5,050/microliter with 78% abnormal lymphocytes, hemoglobin 6.8 g/dl, platelets 4.8 x 10(4)/microliter, and soluble IL-2 receptor 97,600/ml. The abnormal cells were characterized by a hairy appearance under phase contrast microscopy, and showed strong tartrate-resistant acid phosphatase activity. Immunophenotype analysis revealed that these cells were positive for CD11c, CD19 and CD25, and negative for CD5. Bone marrow biopsy showed diffuse proliferation of hairy cells with moderate myelofibrosis. We diagnosed the patient as having European-American-type hairy cell leukemia. Pentostatin was administered at a dose of 5 mg/m2 weekly. After twelve doses, the peripheral blood data returned to the normal range with no hairy cells in the blood or bone marrow, although slight splenomegaly remained. The patient underwent splenectomy in December of the same year, and we were unable to find any hairy cells by histological and immunohistochemical examination. Although most patients with hairy cell leukemia in Japan have the Japanese variant, and the European-American type is rare, pentostatin is as effective as it is for European and American patients.     

Platelet-adjusted IFN dosage in the treatment of advanced hairy cell leukemia

Summary It has been demonstrated that hairy cell leukemia (HCL) can be efficiently treated by various preparations of alpha interferons (IFN). Nevertheless, there are several open questions, such as the route, mode and dosage of IFN application. These variables of IFN treatment may be critical since a myelosuppressive effect of IFN, which is commonly seen in the initial phase of treatment, can result in further deterioration of the already impaired platelet production in advanced HCL. The present study shows that serious side effects can be avoided and the flulike syndromes described by others almost completely reduced by s.c. application of IFN via a portable pump during a daily 8 h period. IFN is initially given five times a week and the daily dose is adjusted according to the actual platelet count. The efficiency controls show that the increase of platelets in the peripheral blood, which is most critical in advanced HCL, may be seen earlier by this than by other protocols, which usually recommend higher daily doses of IFN and only three instead of five weekly applications.     

Recombinant alpha-2 interferon in the treatment of hairy cell leukemia

We treated 14 patients with hairy cell leukemia, 13 of whom had progressive disease, with recombinant alpha-2 interferon administered sc at 2 X 10(6) units/m2, three times per week. Thirteen patients were evaluable for response. All evaluable patients responded within 6-8 weeks. After a minimal treatment duration of 6 months and a maximal of 12 months, three patients have achieved complete response and ten have achieved partial response. With a median treatment duration of 10 months, the responding patients' hematologic parameters are continuing to improve, and no responding patients have relapsed. This outpatient self-administered regimen is well-tolerated, with mild fever, myalgias, and headache usually resolving within 2 months. Although the optimal regimen and the mechanism of action are unknown, recombinant alpha-2 interferon may be the treatment of choice for patients whose disease progresses after splenectomy or who are not surgical candidates.     

Hairy cell leukemia successfully treated with deoxycoformycin]

A 45-year-old male was hospitalized on September 2, 1989 with chief complaints of general fatigue and fever. Physical examination revealed hepatomegaly and massive splenomegaly. Laboratory tests on admission showed Hb of 7.5g/dl, PLT 4.8 x 10(4)/microliters and WBC 9,610/microliters with 81% hairy cells. Bone marrow aspirate demonstrated 55.1% hairy cells and moderate myelofibrosis. Cytochemically, hairy cells were positive for tartrate-resistant acid phosphatase (TRAP). Surface markers were SmIg G+ A+ kappa +, CD11b+, CD11c+, CD19+, CD20+, CD21-, CD25+, HC2+, HLA-DR+. From these findings, a diagnosis of hairy cell leukemia (HCL) was made. After administration of deoxycoformycin (DCF) at a dose of 5.0mg/m2 1-2 times monthly, splenomegaly disappeared, as did hairy cells from the peripheral blood. Hematological level returned to within normal range except for the presence of 1.2% hairy cells and mild myelofibrosis in bone marrow aspirates. DCF has so far been effective for this patient. While DCF has been reported to be effective in the treatment of HCL in the West, it has not been determined in Japanese patients with HCL, who have different hematologic features from those of HCL patients in the West.     

Low-dose cladribine for symptomatic hairy cell leukaemia

Cladribine is an effective therapy for hairy cell leukaemia (HCL), but the standard regime is frequently complicated by neutropenic fever and prolonged T-cell depression. We studied 102 patients with active HCL following treatment with various doses of cladribine given for 7 d. Two patients received 1 mg cladribine/m²/d without toxicity or effect. Eight subsequent patients received 2 mg cladribine/m²/d, and normalized cytopenia as quickly as 94 control patients receiving a standard dose (3.4mg/m² or 0.085 mg/kg), with significantly less lymphopenia and a similar complete remission rate.     

Successful treatment of hairy cell leukemia with beta-ser interferon

Twelve patients with hairy cell leukemia underwent treatment with beta-ser interferon, a type I interferon with potent antiproliferative activity. Ten of the 12 patients had had prior therapy and the median time from diagnosis to initiation of treatment was 8.5 months (range 1 month to 18 years). Bone marrow involvement ranged from 90-100% hairy cells. Beta-ser interferon was administered as an intravenous injection of 90 million units per dose, three times weekly. Dose reductions were by dose and by frequency in individual patients. Ten of 12 patients (83%) responded, including 7 complete (CR) and 3 partial (PR) responses. The median time to at least PR was 6 months and the median time to CR was 12 months. The median duration of overall response (PR + CR or PR) is 31+ months (range 26(+)-40+ months). Of the 6 patients who underwent dose reductions due to toxicity or poor tolerance, 4 CR patients reverted to PR, and 2 PR patients have increased the number of hairy cells in the marrow, while maintaining normal peripheral blood counts. One each of these has regained CR and PR status after an increase in dose.     

2-Chlorodeoxyadenosine (cladribine) in the treatment of hairy cell leukemia and hairy cell leukemia variant: 7-year experience in Poland

Abstract: Between January 1991 and December 1997, 103 patients, 97 with typical hairy cell leukemia (HCL) and 6 with HCL-variant (HCL-V) were treated with 2-chlorodeoxyadenosine (2-CdA) given as 2-h infusion for 5 consecutive d at a daily dose 0.12 mg/kg. To our knowledge this is the largest cohort of HCL patients treated with this type of regimen. Median follow-up amounted to 36 months. Fifty-six of 97 patients with typical HCL were newly diagnosed and 41 were relapsed after previous treatment. Splenectomy as a first-line therapy was performed in 23 patients and 18 remaining patients received prednisone, chlorambucil or interferon-α (IFN-α) alone or in combinations. Seventy-five (77.3%) patients entered CR and 18 (18.6%) achieved PR, giving an overall response rate of 95.9%. The mean time of first CR duration amounting to 32 months (range 3–72) did not correlate to the number of 2-CdA cycles. 2-CdA was equally effective in treatment of newly diagnosed patients and patients who relapsed after previous therapeutic procedures. Relapse of the disease occurred in 20 of 75 patients who achieved CR after 2-CdA and was usually manifested by very discrete changes in peripheral blood counts (neutropenia and/or relative lymphocytosis). The mean progression-free survival (PFS) time in this group was 37.4 (range 10–66) months. Ten of 20 relapsed patients were retreated with 2-CdA given an identical course to the first one. Seven patients entered second CR lasting 19+ (range 8–47) months and 3 experienced PR. This confirms the previous observations that 2-CdA gives no resistance to leukemic clone. Ten remaining patients have not required retreatment so far and remain in a good clinical and hematological state. The results of HCL-V treatment with 2-CdA were poor. Only 2 patients achieved PR and 4 patients did not respond to this drug. Seven patients (5 with typical HCL and 2 with HCL-V) died, 3 of causes unrelated to the disease. Second neoplasms were noted in 5 patients. 2-CdA-related side effects resulted mainly from myelosuppression and infectious complications. In conclusion we confirm the effectiveness of 2-CdA in inducing CR in patients with typical HCL, but this drug is unable to completely eradicate the leukemic clone which results in the relapse of the disease. The real incidence of the relapse rate may be underestimated unless bone marrow biopsy is performed. The results of our study indicate that a 2-h infusion of 2-CdA in HCL patients is at least as effective as a 24-h infusion but more convenient to the patients, and may be given on an outpatient basis.     

Bone marrow morphology during alpha-interferon treatment in hairy cell leukemia

14 patients with HCL were started on alpha-interferon (IFN) treatment. Bone marrow changes were followed in trephine biopsies every 3rd month. Differential counting was performed according to the point counting method and fiber content was evaluated. At the start of treatment all patients had 80% or more of tumor cells in the bone marrow. The reduction of granulopoiesis was more pronounced than for erythropoiesis. During treatment cellularity decreased in 6/13 patients already after 3 months; later, cellularity was normalized in most patients. Only 1 patient showed a complete remission. 12/14 patients showed a significant but slow reduction of tumor cells. Also, between 12 and 18 months an improvement was seen in some patients. The megakaryocytes improved rapidly and the erythropoiesis was normalized before the granulopoiesis. Only 1 patient did not show a bone marrow response. 5/14 patients showed a reduction of bone marrow fibers, first seen after 6 months of treatment. IFN was discontinued in 9/14 patients. 7 of these relapsed during the observation period (18 months).     

Bone lesions in hairy cell leukemia: Diagnosis and treatment

Skeletal involvement is a rare complication of hairy cell leukemia (HCL) with an incidence of approximately 3%. Bone lesions are commonly lytic, and the most common sites of involvement are the femoral head and neck. Skeletal involvement is typically associated with high tumor burden and bone marrow infiltration. However, isolated cases of skeletal disease without splenomegaly or bone marrow involvement are occasionally reported. This review focuses on skeletal lesions in HCL, particularly the pathogenesis, clinical symptoms, diagnostic methods, and treatment approach. A literature review of the MEDLINE database for articles in English concerning hairy cell leukemia, skeletal symptoms, bone involvement was conducted via PubMed. Publications from January 1970 to May 2020 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles.     

Diffuse osteosclerosis in hairy cell leukemia

We describe two patients with a new clinical pathologic syndrome of diffuse osteosclerosis in association with hairy cell leukemia. In both patients bone marrow biopsies could not be obtained due to extremely hard bones and inability to insert the biopsy needle; neither patient had a history of bony pain or fracture. The osteosclerotic process in one patient stabilized after successful treatment of her hairy cell leukemia with interferon alpha and deoxycoformycin suggesting that the osteosclerosis observed was related to the underlying malignant disease. Possible etiologic mechanisms are discussed.     

A hairy B cell lymphoproliferative disorder resembling hairy cell leukemia

This case report describes a hairy B cell lymphoproliferative disorder (HBLD) with clinical and hematological features resembling hairy cell leukemia. The patient was a 29-year-old female who demonstrated atypical lymphocytes in her peripheral blood. Physical examination demonstrated splenomegaly, but there were no palpable superficial lymph nodes. Hematological examination showed a leukocyte count of 10.6 x 10(3)/mm3 with 41% atypical lymphocytes. Bone marrow examination showed a normal cellular and an atypical lymphocyte count of 42%. The atypical lymphocytes had microvilli and prominent membranous ruffles on their surfaces. Atypical lymphocytes expressed CD5- CD10- CD11c+ CD19+ CD20+ CD23- CD25- on the surface of the cells on examination by with a fluorescence activated cell sorter. Although these findings were similar to hairy cell leukemia, Japanese variant, the surface marker of the kappa chain and lambda chain was unbiased and studies of immunoglobulin gene rearrangements and expression showed polyclonal proliferation of B cells. Therefore, we diagnosed this patient as having HBLD. Because she did not demonstrate anemia or thrombocytopenia, she is not currently receiving medication. To date, the atypical lymphocyte count has not changed.     

Hemopoietic inhibition in hairy cell leukemia

Leukopenia, thrombocytopenia, and anemia are important features of hairy cell leukemia (HCL). They are generally considered to be due to hypersplenism and to inadequate production by bone marrow which is heavily infiltrated by the neoplastic hairy cells (HC). However, the cytopenias may also be caused by hemopoietic inhibition by cytokines derived from the mononuclear cells (MNC) of HCL. We studied the MNC of HCL with an in vitro assay for granulocyte-macrophage progenitors (CFU-GM) to search for this hemopoietic inhibitor(s) and to determine the cell source and mechanism of its production/release. We found that MNC conditioned media from 7 of 9 HCL cases exerted substantial inhibitory effect (23% to 66%) on normal marrow cells. Peak inhibitory activity was obtained in media conditioned with 10(6) MNC/ml for 90 minutes to 24 hours. Both HC and lymphocytes could release inhibitor(s) through mutually synergistic cell interactions. HC alone were inactive and lymphocytes alone were only weakly active. Mixtures of conditioned media of HC and of lymphocytes were not synergistic. The lymphocytes responsible for the inhibition were present in preparations depleted of cells bearing the cluster designation 4 antigen (CD4+) and B cells and were most likely the CD8+ T-cells. In one patient so examined, a partial reversal of inhibition was achieved by treating MNC-CM with antibodies to tumor necrosis factor (TNF)-alpha suggesting that TNF-alpha was at least partly involved in the inhibition of CFU-GM. This mechanism of cytokine release may be operative in vivo to account for the cytopenias in HCL and, if so, could alter the concept of hypersplenism in this disease.     

Bone involvement in hairy cell leukemia

Four patients with a diagnosis of hairy cell leukemia complicated by bone involvement are described. This is an uncommon complication of the disease. Manifestations included osteolytic lesions, severe osteoporosis, and aseptic necrosis of the femoral head. The osseous complications do not seem to bear on the prognoses for these patients. Radiotherapy or chemotherapy provides symptomatic relief and may prevent further morbidity from the bone lesions.