Acute leukemia: Diagnosis and management of testicular involvement

Contemporary therapy of acute leukemia frequently achieves long-term continued complete remission (CCR) of bone marrow disease and prevents central nervous system relapse. However, accompanying improved survival is an increasing incidence of overt testicular relapse either during CCR or associated with bone marrow relapse. In 7 boys testicular abnormalities developed during CCR, 6 had open biopsy and 5 had histologically confirmed leukemic infiltration. Despite local therapy of orchiectomy or irradiation and chemotherapy reinduction, 2 of 6 had testicular relapse and 4 of 6 died. Three boys with coexistent overt testicular and systemic relapse died. Nine boys with normal testes had testicular biopsy during CCR prior to discontinuation of chemotherapy. Results of all biopsies were benign, but one boy had a relapse. The diagnosis of occult testicular leukemia prior to discontinuation of chemotherapy allows selection of high-risk boys requiring prolonged, intensive, and possibly alternative therapy. The indication for testicular biopsy in boys with acute leukemia is documented, and appropriate clinical management of testicular leukemia is presented.     

Use of fine needle aspiration cytology for the diagnosis of testicular relapse in patients with acute lymphoblastic leukemia

The testis frequently is the site of relapse in male patients with acute lymphoblastic leukemia. While many patients with testicular involvement by acute lymphoblastic leukemia have enlarged or firm testes, clinical examination alone is insufficient to establish or exclude the diagnosis completely. Open biopsy generally has been used to document the presence of acute lymphoblastic leukemia. However, this procedure requires general anesthesia and hospitalization. We studied 11 patients with a history and/or physical findings suspicious for testicular acute lymphoblastic leukemia relapse to determine the efficacy of fine needle aspiration cytology in the evaluation of the testes for leukemic infiltration. Of the 11 patients fine needle aspiration cytology correctly identified all 5 patients with histologically proved testicular acute lymphoblastic leukemia, it was negative in 5 with no histological evidence of leukemia and it demonstrated rare atypical cells that were not evident on subsequent histological examination in 1. No adverse effects were encountered in this series. Fine needle aspiration cytology appears to be a safe, reproducible alternative to open biopsy in the evaluation of patients for testicular relapse of acute lymphoblastic leukemia.     

Testicular infiltrate in childhood acute lymphocytic leukemia The need for biopsy in suspected relapse

The testicle is a prime initial target for infiltration during relapse in male children with acute lymphocytic leukemia. Herein we report our experience with management of this entity in 8 children. It is stressed that a biopsy is essential to the diagnosis. The differential diagnosis is usually straightforward. One is admonished not to make presumptive diagnosis by palpation. Orchiectomy is unwarranted. The treatment of choice is testicular radiation with 2,000 rads in ten fractions in a twelve-day course plus reinstitution of high-dose adjunctive chemotherapy in those children off chemotherapy, or reinduction therapy for children who relapse while still on chemotherapy. Prognosis of male children who undergo a bout of testicular infiltration is guarded.     

Isolated testicular leukemic relapse. Response to radiation therapy

Between January, 1975, and December, 1984, at the University of Michigan Medical Center, 17 boys with leukemia presented with overt or occult isolated testicular relapse. Diagnosis was obtained by bilateral open-wedge biopsies of the testes. All the patients were treated with combined local testicular irradiation and systemic chemotherapy. In only 1 of the 17 patients (6%) testicular leukemia developed as the only site of relapse. It appears that doses in the range of 2,000 to 2,400 cGy in 10 to 12 fractions achieve optimum control of leukemic infiltration of the testes.     

Childhood leukemia presenting with back pain and vertebral compression fractures

Vertebral body collapse and back pain are an unusual presentation for childhood leukemia. This report is intended to promote greater awareness that acute lymphocytic leukemia can cause significant back pain in children without other systemic symptoms. We describe four cases in which patients with acute lymphocytic leukemia presented with back pain and vertebral compression fractures. All of the patients were initially misdiagnosed. No patient had neurologic compromise, despite extensive vertebral body collapse. The back pain was relieved after chemotherapy.     

Ovarian tumors in relapsing acute lymphoblastic leukemia: a review of 23 cases

Five cases of relapsing acute lymphocytic leukemia (ALL) presenting as an ovarian tumor have been treated at this institution, representing the largest reported series. In a review of the literature we identified 18 additional cases of ovarian leukemic relapse. Together, these 23 patients form the basis for this report. Abdominal pain is the most common presenting symptom of ovarian leukemia. An abdominal mass is usually palpable, and at least four patients had hydronephrosis. Nine patients had documented bilateral ovarian involvement; however, bilateral disease was not a poor prognostic sign. Most ovarian relapses occurred more than 36 months after the original diagnosis of ALL, with these "late'h relapsers responding more favorably to treatment than "early" relapsers. Definitive statements can not be made from a retrospective review of 23 case reports; however, salpingooophorectomy had no obvious advantage over simple biopsy, and there was no obvious advantage to the routine use of radiation therapy. Most failures in treating ovarian leukemia occurred within 2 years. Most failures were systemic rather than local, illustrating the need for aggressive multiagent systemic chemotherapy. Survival after ovarian leukemic relapse is possible, with eight of the 23 patients alive and in complete continuous remission following the ovarian relapse (median follow-up since relapse, 42 months; range, 2 to 135+ months). With the use of more intensive chemotherapy in recent protocols, the frequency of ovarian leukemic relapses appears to be decreasing. At this institution, no child with ALL diagnosed in the 1980s has subsequently developed an ovarian relapse.     

Needle biopsy in the diagnosis of testicular leukemia in children

Aggressive chemotherapy in patients with acute lymphoblastic leukemia has resulted in a marked upsurge in patient survival. In the course of their management, testicular biopsy and rebiopsy have an important role. We evaluated the histological findings in 50 sets of open wedge and simultaneous needle core biopsy specimens from 44 testes of children with acute lymphoblastic leukemia to determine the accuracy of the needle biopsy technique in the evaluation of testis involvement in acute lymphoblastic leukemia. We conclude that needle biopsy of the testis in acute lymphoblastic leukemia is highly accurate and correlates well with the conventional open wedge biopsy, and it may have a role in the management of children with acute lymphoblastic leukemia.     

Cardiac involvement in a case of acute lymphoblastic leukemia

We present an extremely rare case of an immunocompromised patient with a T-cell acute lymphocytic leukemia relapse presenting as a right atrial tumor. Problems in diagnosis, vulnerability due to previous immunosuppression and bone marrow transplant, and successful surgical excision are highlighted. Cardiac involvement with hematologic neoplasms should be taken with more than academic interest, as it may be amenable to treatment.     

Noninvasive testicular screening in childhood leukemia

To evaluate the potential of transscrotal ultrasound and magnetic resonance imaging as noninvasive screening methods we studied 8 boys with acute lymphocytic leukemia before testicular biopsy. Ultrasonic images of the testes were performed in 4 patients, including 2 with negative and 2 with positive biopsies, and all images were interpreted as normal. Magnetic resonance images of the testes also were interpreted as normal in 4 patients, including 2 with negative and 2 with positive biopsies, and they were technically inadequate in the remaining 4. The results suggest that neither transscrotal ultrasonography nor magnetic resonance imaging as currently applied may substitute reliably for testicular biopsy as a screen for occult testicular leukemia.     

Prostatic extramedullary leukemia as a first site of relapse of acute nonlymphocytic leukemia

Extramedullary leukemia (EML) is an uncommon clinical diagnosis in patients with acute nonlymphocytic leukemia (ANLL). Prostatic EML as a first site of ANLL relapse is even more rare. To our knowledge, only three cases have been reported. We describe an additional case of prostatic EML as a site of ANLL relapse. An asymptomatic male in ANLL remission was found to have a normal prostate-specific antigen (PSA) and a myeloid leukemic infiltrate in a newly diagnosed prostate nodule. Staging was negative for ANLL relapse. Local prostate radiation resolved the nodule, and the post-treatment needle biopsies were negative. He subsequently developed clinical relapse in bone marrow, blood, and small bowel and received salvage chemotherapy with mitoxantrone and etoposide.     

Demonstration of a leukemia-associated antigen (CAMAL) in peripheral blood leucocytes of bone marrow transplant patients prior to relapse

We have previously described a monoclonal antibody (CAMAL-1) that reacts in an indirect immunoperoxidase slide test at high frequency with cells of patients with acute nonlymphoblastic leukemia (ANLL), both at presentation and in remission (1). This article reports on a 12-month blind study carried out on peripheral blood leukocytes (PBL) of patients who had received bone marrow transplants for acute leukemias. PBL of patients attending the Royal Marsden Hospital were sent as cytospins to the University of British Columbia for staining and screening. Results of this study showed the following: of the 15 patients who remained in remission during the period of the study, 13 showed no abnormal increase in reactivity with CAMAL-1 (2 patients did show increased levels of reactivity over time); of the four patients relapsing but surviving within this period with ANLL, all showed elevated numbers of cells reactive with CAMAL-1 as long as 3 months prior to relapse (the two relapsing patients who had acute undifferentiated leukemia and acute lymphoblastic leukemia did not show elevations of CAMAL-1-reactive cells); of the 14 patients dying during this time of causes other than leukemia, none had elevated levels of CAMAL-1-reactive cells--and, of 4 patients dying in relapse, all had extremely elevated levels of CAMAL-1-reactive cells as long as 4 months prior to relapse. The implications of these observations are discussed.     

A case of pulmonary mucormycosis accompanied by lymphocytic leukemia successfully treated by pulmonary lobectomy

A 51 years old man with acute lymphocytic leukemia who was treated with antileukemic chemotherapy, developed sepsis and pneumonia. Secondary infection with Mucor intervened with abscess formation cured by lobectomy. The patient is doing well without evidence of recurrence, and treated successfully with anti-leukemic chemotherapy. Surgical treatment offers the last chance of survival in similar cases.     

T-cell chronic lymphocytic leukemia in a double yellow-headed Amazon parrot (Amazona ochrocephala oratrix)

An adult, male double yellow-headed Amazon parrot (Amazona ochrocephala oratrix) was diagnosed with chronic lymphocytic leukemia based on results of a complete blood cell count and cytologic examination of a bone marrow aspirate. Treatment with oral chlorambucil was attempted, but no response was evident after 40 days. The bird was euthanatized, and the diagnosis of chronic lymphocytic leukemia was confirmed on gross and microscopic examination of tissues. Neoplastic lymphocytes were found in the bone marrow, liver, kidney, testes, and blood vessels. Based on CD3-positive immunocytochemical and immunohistochemical immunophenotyping, the chronic lymphocytic leukemia was determined to be of T-cell origin.     

Postirradiation cerebellar glioma. Case report

A 13-year-old girl developed an anaplastic astrocytoma of the cerebellum 7 years after irradiation of the central nervous system and prophylactic chemotherapy for acute lymphocytic leukemia. The fact that the astrocytoma was anaplastic and infiltrative was unusual for astroglial tumors at this site. It is proposed that this is a radiation-induced glioma.     

Delayed neutropenic enterocolitis in a 12-year-old girl treated with total colectomy and J-pouch reservoir.

Neutropenic enterocolitis (NE) is a clinicopathologic condition characterized by bowel wall inflammation, which can proceed to necrosis and perforation. It is mostly seen in neutropenic patients with leukemia who undergo induction treatment with chemotherapy. Most often the cecum is involved. The authors present a 12-year-old girl with acute lymphocytic leukemia who, under maintenance therapy, experienced NE. The disease was localized to the left side of colon, and even the rectum was involved, which is an unusual localization of the disease. An ileoanal anastomosis with a J-pouch was done in a second operation with a good outcome.     

Acute lymphocytic leukemia recurring in the spinal epidural space

A 27-year-old man presented with a very rare spinal epidural mass associated with recurrence of acute lymphocytic leukemia (ALL) manifesting as acute progressive neurological deficits. The patient presented with shoulder pain and ambulatory difficulties 3 years after remission of ALL treated by bone marrow transplantation. Magnetic resonance imaging revealed an epidural mass extending from C-7 to T-3, which compressed the cord and extended to the intervertebral foramen along the roots. After decompression surgery, the symptoms dramatically improved. Histological examination showed clusters of immature lymphocytes consistent with recurrence of leukemia, so chemotherapy and radiation therapy were carried out. At 1 year after the operation, no local mass expansion or systemic progression of leukemia had occurred. Leukemic mass must be considered in the differential diagnosis of spinal epidural mass, even in patients with ALL.     

IgA nephropathy associated with leukemia and lymphoma: report of two cases

IgA nephropathy (IgAN) associated with leukemia and lymphoma has not, to our knowledge, been reported in children. Two children suffering from these diseases are described here. One patient developed IgAN at the end of 5 years’ chemotherapy for acute lymphocytic leukemia. The other had microscopic hematuria 3 years before the onset of non-Hodgkin lymphoma, and hematuria continued during chemotherapy. Each disease occurred after a long interval, and the clinical courses did not run parallel. The association was thought to be incidental in our cases. Chemotherapy with adrenocorticosteroids and immunosuppressants [6-mercaptopurine (6-MP) and cyclophosphamide (CY)] for leukemia and lymphoma did not affect the clinical course of IgAN.     

Childhood leukemia presenting as a diaphyseal radiolucency.

A 41-month-old black child with a symtomatic diaphyseal destructive lesion of the femur, and a corresponding area of increased uptake on a technetium99m bone scan, had an upper respiratory tract infection. An open biopsy was performed because of an initial clinical diagnosis of osteomyelitis, histiocytosis X or a round cell sarcoma. The biopsy showed numerous blast cells compatible with acute lymphocytic leukemia. Acute leukemia should be included in the differential diagnosis of symptomatic diaphyseal destructive lesions in children. A peripheral blood smear should be carefully interpreted prior to any other invasive diagnostic tests.     

Pancreatic pseudocyst complicating treatment of acute lymphoblastic leukemia

In the management of children with acute lymphoblastic leukemia, L-asparaginase has become established as an effective drug in the usual multi-agent therapy; and the significance of pancreatitis as a complication of this drug is well recognized. Less well appreciated, however, is the progression of such pancreatitis in some patients to pseudocyst formation and the possible necessity for surgical management. Two adolescent girls who developed pancreatic pseudocysts while being treated with L-asparaginase are described in this report. Both were being treated for acute lymphoblastic leukemia for periods of 18 and 4 months, respectively, prior to the onset of pancreatitis. Both were in remission of their leukemic disease when typical clinical and laboratory manifestations of acute pancreatitis developed. In one girl, a pancreatic pseudocyst became apparent 2 weeks following the diagnosis of acute pancreatitis and in the other girl, this complication developed over a period of 8 weeks. The usual nonsurgical management of pancreatitis over protracted periods of time was ineffective in the treatment of the pseudocysts. Surgical drainage (internal in one and external in the other) was successful in both in eradicating the pseudocyst, and in neither did further evidence of pancreatic disease subsequently occur. In both resumption of chemotherapy, omitting L-asparaginase, was well tolerated. One has been in remission of leukemia and in good health for a 3-year period of follow-up observation, while the other subsequently had a relapse of leukemia and died 18 months following the onset of pancreatitis.     

HLA半相合造血干细胞移植治疗首次复发的急性髓系白血病

目的 探讨遗传上HLA半相合外周血造血干细胞移植(Haplo-PBSCT)对首次复发后的成人急性髓系白血病(AML)的治疗效果.方法 89例成人AML患者接受常规柔红霉素-高剂量阿糖胞苷(DA/Hi-Ara-C)化疗缓解后出现首次复发,其中复发后接受Haplo-PBSCT治疗者53例,平均年龄38.6岁(18～51岁),复发时间为首次缓解后7.7个月(1～24个月);接受去甲氧柔红霉素-中剂量阿糖胞苷(iDA/Mid-Ara-C)或米托蒽醌-中剂量阿糖胞苷(MA/Mid-Ara-C)方案继续化疗者26例,平均年龄47.6岁(18～61岁),复发时间为首次缓解后8.9个月(1～30个月).结果 接受Haplo-PBSCT治疗者和接受化疗者再次完全缓解率(CR)分别为86.7%(46/53)和38.1%(9/23),两者比较,差异有统计学意义(P＜0.01).接受Haplo-PBSCT治疗者和接受化疗者36个月的疾病进展后存活(SPP)率分别为43.4%(23/53)和11.5%(3/26),两者比较,差异有统计学意义(P＜0.05).结论 相对于接受iDA/Mid-Ara-C或MA/Mid-Ara-C方案继续化疗者,Haplo-PBSCT能明显提高首次复发后AML患者的再次缓解率以及延长SPP时间.

Abstract：

Objective To investigate the therapeutic effects of haploidentical hematopoietic stem-cell transplantation (Haplo-PBSCT) for acute myeloid leukemia in first relapse after complete remission by standard induction chemotherapy. Methods Eighty-nine cases of AML in first relapse after complete remission by standard DA/Hi-Ara-C regimens induction chemotherapy were evaluated retrospectively. Fiftythree cases were grafted by haplo-PBSCT and 26 cases were treated with iDA/Mid-Ara-C or MA/ Mid- Ara-C agents. Results The second remission rate in haplo-PBSCT group and continuous chemotherapy group was 86. 7 % (46/53 cases) and 38. 1% (9/23 cases) respectively (P＜0. 01). Survival postprogression (SPP) at 36th month was 43. 4 % (23/53 cases) in haplo-PBSCT group and 11.5 % (3/26 cases) in continuous chemotherapy group (P ＜ 0. 05). Conclusion Haplo-PBSCT could significantly increase the second remission rate and prolong the survival time of patients with acute myeloid leukernia in first relapse after complete remission by standard induction chemotherapy.