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Twenty-four patients with advanced hairy cell leukemia treated with 2'-deoxycoformycin (dCF) were studied after achieving complete remission to determine the impact of treatment on survival, disease-free survival, long-term complications of treatment, and response to retreatment. At a median follow-up time of 82 months (range, 54 to 104 months), 23 of 24 patients remain alive. One patient has died of recurrent disease refractory to treatment. Of the remaining 23 patients, 11 have relapsed at a median time of 30 months (range, 7 to 80 months) after treatment completion. Of these 11 patients, 7 have been retreated with dCF or 2'-chlorodeoxyadenosine (2-CdA), including one patient that was retreated twice. All seven patients have responded, with five patients achieving second complete remission. Two patients have had normalization of blood cell counts, but repeat bone marrows have not been performed. No serious infections have been seen in dCF-treated patients during follow-up. One case of Hodgkin's disease and three cases of skin malignancies have developed in these 24 patients. From initiation of treatment, survival is 93 months (range, 63 to 116 months). We concluded that dCF significantly prolongs the survival of patients with advanced hairy cell leukemia without resultant long-term complications. It is too early to predict if this therapy will be curative for the patients still in remission.

Since 1958, when HCL was first recognized as a new clinical, hematologic and pathological entity, great progress has been made through the contributions of numerous investigators: The hematopathology of the hairy cell and the organs involved by the disease have been well established. The early controversies concerning the cellular origin of the hairy cell has been clarified and is now recognized that the hairy cell of HCL is of B-lymphocyte lineage. The position of the hairy cell within the spectrum of B-cell chronic lymphoproliferative-disorders indicates that the CLL-lymphocyte is in an early stage and the hairy cell of HCL in a later stage in mature B-cell development. The hairy cell represents an activated B-CLL lymphocyte. The comparison of the immunophenotyping patterns of HCL and the other lymphoproliferative disorders is being clarified. Monoclonal antibodies raised against hairy cells or with restricted specificity for hairy cells, as well as other biological markets such as IL-2 and TNF, are being used for monitoring response to treatment and detecting minimal residual disease. In the last decade, major advances have been made in the treatment of HCL with the advent of interferon and the nucleosides. Our goal today is to achieve a complete response of prolonged or permanent duration. For this reason: Splenectomy, has only a few indications at present. After 10 years of experience with the interferons it is recognized that interferon induces a few complete responses and all patients eventually relapse. Currently the nucleosides: dCF and 2-CdA are the first line of treatment of HCL. Both drugs have acceptable toxicity and induce complete remissions in the majority of patients. However, longer periods of observation are needed to establish the duration of response and to document if any patients will attain a cure by the nucleosides. In the continuation of the progress in achieving our goals, we definitely need: better parameters for the evaluation of complete response and detection of minimal residual disease: to search for the characteristics for prediction of response to therapy; long-term randomized studies between dCF and 2-CdA as an initial therapy, as well as randomized treatment of relapsed patients to determine the incidence of reinduction or cross-resistance. Meanwhile the work has to continue with the development of newer strategies and of new drugs, if our goal of cure of HCL patients is to be attained.

This is a Southwest Oncology Group (SWOG) prospective randomized trial of cisplatin, vinblastine, and bleomycin (PVB) versus vinblastine, cisplatin, and etoposide (VP-16) (VPV) in the treatment of advanced germ cell tumors of the testis. The study objective was to determine what effect the replacement of bleomycin with VP-16 has on complete response (CR), survival, and drug toxicity. One hundred sixty-nine patients were registered and randomized. Of these patients, 160 were assessable for response. All had histologically confirmed disseminated germ cell neoplasms of testicular origin. Forty-six had minimal metastatic disease, and 114 had maximal disease. Seventy-seven were randomized to PVB and 83 to VPV chemotherapy. There was no significant difference in pretreatment characteristics between the two arms with regard to tumor burden, histologic type, and overall performance status. Patients received four courses of induction chemotherapy, either PVB (cisplatin 120 mg/m2 day 3, vinblastine 12 mg/m2 day 1, bleomycin 15 U/m2 twice per week) or VPV (vinblastine 8 mg/m2 day 1, cisplatin 120 mg/m2 day 3, VP-16 50 mg/m2 days 2 to 5). Chemotherapy was given every 3 weeks. Cytoreductive surgery was done postinduction if a chemotherapy CR was not achieved. There was no difference in the percentage of patients achieving a disease-free status between PVB (77%) and VPV (73%). The mean leukocyte nadir was similar for both treatments, but the mean platelet nadir was significantly lower (P = .003) in the VPV arm. All bleomycin-related toxicities (pulmonary, mucositis, skin) were avoided in the VPV arm. We conclude that bleomycin can be replaced in first-line therapy for advanced germ cell tumors without sacrificing efficacy and with the advantage of avoiding unnecessary drug toxicity.

Ten patients with progressive hairy cell leukemia were treated with 2′deoxycoformycin (dCF) by intravenous bolus (4 mg/m2) given every other week. All ten patients are evaluable for response and nine of the ten patients have achieved a complete remission. In addition to clearing of hairy cells from the bone marrow, eight patients had resolution of their monocytopenia. Seven of the nine patients remain in unmaintained remission with a median duration of 6.2 months. Two patients have had relapse in the bone marrow alone and continue to have normal peripheral blood counts. They are being followed without treatment. Toxicity was minimal at this low dose with one patient having a mild reversible reduction in creatinine clearance. Four other patients had reversible neutropenia. There were no significant infections associated with treatment. Low-dose deoxycoformycin administered intravenously every other week represents an extremely effective treatment for hairy cell leukemia.

In a series of 116 patients with hairy cell leukemia at the Ohio State University, followed for over 20 years, several unusual presentations and complications were encountered. The awareness of these unusual findings might be of help to investigators in the prompt diagnosis and treatment of this disease. The patients presented had, at the time of initial diagnosis, spontaneous rupture of spleen, cryptococcal meningitis, massive splenomegaly with hairy cell infiltration with normal peripheral blood and bone marrow examination, and marked leukocytosis. Some patients developed unusual complications during the course of their illness, such as gastric submucosal infiltration by hairy cells with secondary protein-losing enteropathy, spinal cord compression with paralysis, esophageal perforation with fistula tract, and massive ascites and pleural effusion with typical hairy cells present in the ascitic and pleural fluid.

Twelve evaluable patients with progressive hairy cell leukemia were treated with deoxycoformycin at a dose of 4 mg/m2 every 2 weeks. Five patients had not been splenectomized, and one had failed to respond to interferon-alpha. Complete remission, as defined by absence of hairy cells in the bone marrow and normalization of the peripheral blood and regression of splenomegaly, was obtained in 11 of 12 patients (92%). These patients have remained in unmaintained remission for 1+ to 13 months with an average of 7.5 months. Two of these patients had a bone marrow relapse at 8 and 12 months, respectively. During treatment the monocytopenia corrected, and, after complete remission was obtained, marrow was aspirable. Toxicity was mild and reversible. There were no significant infections associated with this treatment. It was of interest that we could treat two patients with creatinine clearance of 50 and 60 ml/min using lower doses (and 2-3 mg/m2) than our conventional therapy of 4 mg/m2 every 2 weeks. They obtained a complete remission after 6 and 10 treatments, respectively. Low-dose deoxycoformycin has proven to be an excellent treatment for hairy cell leukemia.