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.     

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.     

Extramedullary relapse of acute lymphoblastic leukemia in childhood to the prostate

A 6-year-old boy presented with the chief complaints of miction pain and pollakisuria. He had a past history of acute lymphoblastic leukemia (ALL), which subsided in response to chemotherapy at 3 years of age. Ultrasonography revealed urinary retention associated with bilateral hydronephrosis secondary to the prostate enlargement. Computed tomography and magnetic resonance imaging showed no other abnormal finding. Transrectal needle biopsy showed infiltration of leukemic cells in the prostate. Bone marrow puncture and cerebrospinal fluid aspiration revealed no leukemic cells, resulting in a diagnosis of extramedullary relapse of ALL in the prostate. Although he was successfully treated by chemotherapy, irradiation and his voiding function was improved, ALL relapsed in the left testis 1 year later. In spite of left orchiectomy, irradiation and additional chemotherapy, he died of bone marrow relapse and multiple organ failure. Extramedullary relapse of ALL in the prostate is very rare. To our knowledge, our case is the first well-documented report in the published work.     

超声引导系统活检筛查前列腺癌的临床意义

目的 探讨B超引导下前列腺穿刺筛查前列腺癌的临床意义。方法 采用6针系统活检加结节处2－4针活检,197例前列腺特异抗原（PSA）＞4ng/ml或有前列腺结节的患者行 超声引导下前列腺穿刺活检,对4例PSA持续升高者行重复穿刺。结果 有结节者107例中发现前列腺癌34例（31.8%),90例无结节者中发现前列腺癌11例（12.2％）。分析显示：PSA越高,穿刺活检阳性率越高。重复穿刺者4例中发现前列腺癌1例。结论 对有前列腺结节或PSA＞4ng/ml的前列腺增生患者应行系统活检以筛查前列腺癌,穿刺阴性后如PSA持续 增高则应重复穿刺。     

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.     

Immunotoxins for ex vivo marrow purging in autologous bone marrow transplantation for acute nonlymphocytic leukemia

Two potent antimyeloid immunotoxins (IT) were generated by conjugating AML-2-23 (anti-CD14) and MCS-2 (anti-CD13) monoclonal antibodies (mAb) to the ribosome-inactivating phytotoxin, ricin. Both IT selectively bound to target cells, inhibited protein synthesis, and prevented the clonogenic growth of fresh marrow blasts from acute nonlymphocytic leukemia patients as well as KG-1 (ANLL) cells. Cryopreservation did not inhibit IT activity. We conclude that AML-2-23-ricin and MCS-2-ricin show potential for effective ex vivo marrow purging in autologous bone marrow transplantation (ABMT) for ANLL. To our knowledge, this study represents the first evidence of the clinical potential of IT in high-risk ANLL.     

Testicular lymphoblastic leukemia/lymphoma

Summary Acute lymphoblastic leukemia is by far the most frequent malignant disease in children. In all, 5% of the boys affected will develop testicular disease either at initial presentation or during the disease course or as the first site of relapse. Modern treatment regimens have reduced the occurrence of testicular relapses, which was more frequent in the 1970s. There is no place for preventive measures for early recognition of testicular leukemia; routine biopsies have been abandoned, and prophylactic irradiation is not justified. In gross overt disease, orchiectomy is justified (1) in cases of huge bulky testicular disease, (2) if unilateral disease is probable, and (3) if radiation of the testes is refused. In malignant non-Hodgkin's lymphoma, orchiectomy may eventually be the best mode of diagnosing the disease if a boy presents with testicular enlargement. Standard local treatment, however, is irradiation of both testes, if both are affected.     

Technology insight: monoclonal antibody imaging of prostate cancer

Imaging is a critical component of diagnosis, staging and monitoring, all of which factor heavily in treatment decision-making for cancer patients. Agents, such as antibodies, can target molecules that are relatively unique to cancer cells. Prostate-specific membrane antigen (PSMA) is the most well-established, highly restricted prostate-cancer-related cell membrane antigen known. Ten years ago, the FDA approved (111)In-capromab pendetide for use in imaging soft-tissue, but not bone, sites of metastatic prostate cancer for presurgical staging or the evaluation of PSA relapse after local therapy. For presurgical patients with high-risk disease but negative bone, CT and MRI scans, capromab demonstrated the ability to identify some patients with positive nodes, thereby sparing them an unnecessary surgical procedure. But there have been no follow-up studies to indicate that high-risk patients with a negative capromab scan have a lower failure rate after surgery. In the setting of PSA relapse, capromab is compromised by its inability to sensitively image bone metastases; bone is the first site of metastatic prostate cancer in 72% of patients. The problem with imaging bone metastases is that capromab detects an antigenic site on the intracellular portion of PSMA-a site not accessible to circulating antibodies. Early results indicate that second-generation antibodies that target the extracellular domain of PSMA might provide significant benefits in the imaging of prostate cancer.     

伊曲康唑口服液对急性白血病化疗后粒细胞缺乏期侵袭性真菌感染的预防作用

目的评价伊曲康唑VI服液对预防急性白血病化疗后粒细胞缺乏（粒缺）期侵袭性真菌感染（IFI）的疗效。方法回顾性分析2008年1月-2010年12月南方医院血液科收集的急性白血病化疗后伴粒缺的136例患者,将其分为伊曲康唑组（67例）和对照组（69例）。伊曲康唑组中急性非淋巴细胞白血病（ANLL）36例,急性淋巴细胞白血病（ALL）31例;对照组中ANLL30例,ALL38例,1例为急性双表型白血病（BAL）。伊曲康唑组化疗后粒缺期间给予伊曲康唑口服液,持续至中性粒细胞计数〉0．5×10^9／L,或是体温正常且影像学无IFI改变时停用。采用SPSS13．0软件分析两组IFI的发生率及临床特点。计数资料采用PearsonX。检验,正态分布的计量资料采用t检验,偏态分布的数据采用Mann—WhitneyU检验。结果伊曲康唑组12例发生IFI,发生率为17．9％（12／67）,对照组32例发生IFI,发生率为46．4％（32／69）,两组IFI发生率比较差异有统计学意义（X^2=12．59,P〈0．01）。伊曲康唑组中ANLL患者IFI发生率（6／36,16．7％）低于对照组中ANLL患者的发生率（17／30,56．7％）（X^2=11．53,P〈0．01）。伊曲康唑组女性患者IFI发生率（3／35,8．6％）低于男性（9／32,28．1％）（X^2=4．35,P〈0．05）,同时也低于对照组中女性患者IFI发生率（17／38,44．7％）（X^2=11．98,P〈0．01）。结论急性白血病化疗后粒缺期患者预防性口服伊曲康唑可以有效降低IFI的发生,对于急性非淋巴细胞白血病女性患者,疗效更加显著。     

Prostatectomy in patient with leukemia

We have reviewed our experience with 10 patients who had leukemia and prostatic obstruction. Most of these patients had chronic lymphocytic leukemia, and all were stable. Following routine preoperative evaluation all underwent transurethral resection of the prostate (TURP). Two patients (20 per cent) had leukemic infiltration of the prostate. Our series confirms that TURP does not present undue risk to the patient with leukemia if the disease is stable and preoperative evaluation normal.     

非清髓性外周血干细胞移植后白血病复发的防治

目的探讨非清髓性造血干细胞移植后白血病复发的防治。方法7例合并有其它系统疾病的白血病患者接受非清髓性外周血干细胞移植,移植后采用环孢素A及短程甲氨蝶呤预防移植物抗宿主病(GVHD),造血细胞植入后,动态检测骨髓单个核细胞嵌合体的变化,根据嵌合体状态,采用供者淋巴细胞输注(DLI),并配合环孢素A用量的调整来防治白血病复发。结果7例患者移植后造血功能得到恢复,3例移植前合并的疾病有所加重,经处理缓解,移植早期相关并发症少而轻。移植后有3例嵌合体由混合嵌合体(MC)转为完全供者型嵌合体(CC),再转为MC,伴Ph染色体阳性,DLI5~6次后Ph染色体转为阴性,嵌合体状态又转为CC,其中2例发生广泛皮肤慢性GVHD;3例的嵌合体持续为CC,无复发,其中2例接受了1次DLI,此2例在环孢素A减量过程中发生GVHD;1例的嵌合体持续为MC,虽经3次DLI,但无效,患者死于白血病复发。结论非清髓性造血干细胞移植后应动态监测嵌合体状态,采用供者淋巴细胞输注,并配合环孢素A用量的调整,对白血病的复发有一定的效果。     

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.     

The actual value of the surgical margin status as a predictor of disease progression in men with early prostate cancer

OBJECTIVES: The surgical margin status after radical prostatectomy for prostate cancer has long been considered a powerful prognostic factor, as well as an important risk factor for local recurrent disease after radical prostatectomy. In this study, a critical analysis of the predictive value of the surgical margin status was performed. METHODS: A well-described cohort of 281 participants of a population-based randomized screening trial who underwent radical prostatectomy between 1994 and 2000 was analyzed. Besides pathologic tumor stage, Gleason score, percentage of high-grade cancer, and tumor volume, the prognostic value of the surgical margin status for disease outcome (prostate-specific antigen [PSA] relapse, local recurrence) was statistically evaluated. Specifically, site ('apical' or 'circumferential') and extent of surgical margin negativity ('negative', or 'close') or positivity ('focal' or 'extensive') was assessed. RESULTS: At a median follow-up of 7 yr (range, 5-120 mo), 39 (13.9%) and 7 (2.5%) men had biochemical failure (PSA >/=0.1ng/ml), and local relapse, respectively. The surgical margin status was positive in 66 (23.5%), with 26 (9.3%) at the prostatic apex. The margin status was an independent statistically significant risk factor for biochemical relapse, though not for local relapse. Of those with positive margins, 22 (33.3%) had PSA relapse and 4 (6.1%) had local recurrence, whereas these figures were 17 (7.9%) and 3 (1.4%) for those with a negative surgical margin, respectively. The extent of margin positivity was not predictive of PSA relapse nor was the site of the surgical margin. CONCLUSIONS: In surgically treated prostate cancer, the surgical margin status has, although being a statistically significant prognostic factor, only limited predictive value for PSA relapse and local recurrent disease. The majority of men with (extensive) positive surgical margins will not experience PSA relapse nor local disease progression, even in absence of adjuvant radiotherapy. So, cases with a positive margin of resection may still be cured, although the procedure in itself was not 'radical'.     

Microscopic pulmonary tumor embolism secondary to adenocarcinoma of the prostate

We report a case of pulmonary tumor embolism involving multiple emboli from an unusual site, an adenocarcinoma of the prostate. A 78-year-old Japanese man was diagnosed with stage IV (1997 version of the TNM classification) moderately differentiated adenocarcinoma of the prostate in December 1997. He underwent bilateral orchiectomy and hormonal therapy with flutamide was started. The patient suffered from relapse in April 1998, and estramustine phosphate was administered as treatment for hormone-refractory prostate cancer. He noticed a dry cough in May 1998, and on June 13, he developed acute progressive dyspnea and was admitted to our hospital. Radiological findings, blood gas analysis, and clinical symptoms suggested pulmonary thrombosis. Despite anticoagulation and oxygen therapy, he remained severely dyspnoeic. He died of respiratory failure 4 days after admission. Autopsy confirmed dissemination of poorly differentiated adenocarcinoma of the prostate to the majority of the pulmonary muscular arteries.     

Strategy for Repeat Biopsy of Patients with Prostatic Intraepithelial Neoplasia Detected by Prostate Needle Biopsy

Purpose

We evaluated the strategy for repeat biopsy of patients with prostatic intraepithelial neoplasia without concurrent carcinoma detected on prostate needle biopsy.

Materials and Methods

Of 1,275 consecutive patients undergoing prostate needle biopsy 61 were identified with prostatic intraepithelial neoplasia but without concurrent prostate carcinoma. Of the 61 patients 53 had undergone repeat biopsy. The medical records, transrectal ultrasound, and operative and pathological reports of these patients were reviewed.

Results

Repeat biopsy was done in 53 patients with prostatic intraepithelial neoplasia, yielding carcinoma in 15, prostatic intraepithelial neoplasia without carcinoma in 8 and benign tissue in 30. The yield of carcinoma from repeat biopsy of a prostatic intraepithelial neoplasia site was 8.3 percent (7 of 84 sites). A total of 18 sites of carcinoma was detected by repeat biopsy of a previous random biopsy site (8), a prostatic intraepithelial neoplasia site only (5), a transrectal ultrasound nodule (3), a palpable nodule and prostatic intraepithelial neoplasia site (1), and a transrectal ultrasound nodule and prostatic intraepithelial neoplasia site (1). Carcinoma was as frequently detected by repeat biopsy of a prostatic intraepithelial neoplasia site (6 patients) as by random repeat biopsy (6 patients).

Conclusions

Repeat prostate needle biopsy of patients with prostatic intraepithelial neoplasia should include random repeat biopsy and repeat biopsy of transrectal ultrasound abnormalities as well as previous sites of prostatic intraepithelial neoplasia.     

Scrotal ultrasonography as adjunct to testis biopsy in leukemia

Testicular involvement in acute lymphocytic leukemia is considered an indicator of extramedullary relapse following chemotherapy. Biopsy of the testes prior to the cessation of chemotherapy has yielded early diagnosis and treatment of relapse, with an improved prognosis. Scrotal ultrasonography successfully guided the biopsy of palpably normal testes in a boy with acute lymphocytic leukemia. This success suggests that ultrasound may be a useful adjunct in localizing occult testicular leukemia prior to biopsy.     

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.     

氟达拉滨联合阿糖胞苷化疗治疗异基因造血干细胞移植后急性白血病复发

目的 观察氟达拉滨联合阿糖胞苷(FA方案)大剂量化疗对异基因造血干细胞移植(allo-HSCT)后急性白血病复发的治疗效果.方法 急性白血病患者10例,7例接受亲缘供者造血干细胞移植,3例接受非亲缘供者造血干细胞移植,所有患者移植后均获得造血重建,为完全供者型.10例于首次移植后38～213 d(中位数为126 d)急性白血病复发,其中完全供者型复发1例,完全受者型复发4例,混合嵌合体型复发5例.原发病复发后均采用FA方案化疗,氟达拉滨用量为25 mg/m2,阿糖胞苷用量为1.5 g/m2,用5 d,其中6例于化疗结束后第2天还接受原供者外周造血干细胞(PBSC)移植,未使用预防移植物抗宿主病(GVHD)的药物.结果 除1例早期(8 d)死亡外,其余9例再次获得造血重建,经外周血DNA序列分析证实为完全供者型.获得造血重建的9例,4例由于复发、感染、多脏器功能衰竭等原因死亡,5例无病存活至随访结束,存活时间分别为585、442、405、213和243 d.治疗后,3例未发生GVHD,其余7例发生急性或慢性GVHD;7例并发肺部真菌感染,3例并发出血性膀胱炎,4例并发巨细胞病毒血症.10例的6个月实际无病存活率为60%,2年预期无病存活率为53%.结论 对于allo-HSCT后的急性白血病复发,采用FA方案化疗,如条件允许联合原供者造血干细胞输注,可能是目前可采取的一种有效治疗方案.     

Loss of mismatched HLA in acute myeloid leukemia relapse after haploidentical peripheral blood stem cell transplantation combined with unrelated cord blood: A case report

Mismatched human leukocyte antigen (HLA) loss is an essential mechanism involved in immune escape and recurrence in acute leukemia after haploidentical transplantation. Patients relapsing after transplantation with HLA loss have a poor prognosis, and are less likely to benefit from donor lymphocyte infusion (DLI) from the original donor. Here, we report a patient with high-risk acute myeloid leukemia who relapsed within six months after haploidentical peripheral blood stem cell transplantation (PBSCT) combined with unrelated umbilical cord blood (UCB) with a session of prophylactic DLI. This patient achieved transient remission after subsequent Interferon-α-1b treatment for two weeks but experienced a second relapse within one month. Genomic analysis by real-time PCR assay revealed that this patient had a loss of an entire mismatched HLA haplotype that was derived from her haploidentical donor. Haploidentical peripheral blood stem cell transplantation with prophylactic DLI might be a triggering event for HLA loss relapse after haploidentical transplantation combined with UCB. HLA loss should be considered in patients with post-HSCT relapse, especially in haploidentical transplantation.